10 July 2014 Tailoring the interplay between electromagnetic fields and nanomaterials toward applications in life sciences: a review
Author Affiliations +
Abstract
Continuous advances in the field of bionanotechnology, particularly in the areas of synthesis and functionalization of colloidal inorganic nanoparticles with novel physicochemical properties, allow the development of innovative and/or enhanced approaches for medical solutions. Many of the present and future applications of bionanotechnology rely on the ability of nanoparticles to efficiently interact with electromagnetic (EM) fields and subsequently to produce a response via scattering or absorption of the interacting field. The cross-sections of nanoparticles are typically orders of magnitude larger than organic molecules, which provide the means for manipulating EM fields and, thereby, enable applications in therapy (e.g., photothermal therapy, hyperthermia, drug release, etc.), sensing (e.g., surface plasmon resonance, surface-enhanced Raman, energy transfer, etc.), and imaging (e.g., magnetic resonance, optoacoustic, photothermal, etc.). Herein, an overview of the most relevant parameters and promising applications of EM-active nanoparticles for applications in life science are discussed with a view toward tailoring the interaction of nanoparticles with EM fields.
del Pino: Tailoring the interplay between electromagnetic fields and nanomaterials toward applications in life sciences: a review

1.

Introduction

Nanoparticles, in the following referred to as NPs, exhibit outstanding physicochemical properties in contrast to their bulk counterparts, i.e., non-nanostructured materials. Indeed, NPs can be considered as fundamentally new materials owing to distinct size-dependent properties, which some materials present in the size range of ca. 1 to 200 nm. In the nanoscale, properties such as size, shape, and crystallinity can dramatically affect the optical, magnetic, and/or catalytic properties of NPs. In general, the spatial confinement of electrons, phonons, and electric fields in and around the NPs determine most of these novel “nano” properties.1 Control of the NP properties allows us to anticipate their response to electromagnetic (EM) fields of a particular frequency and intensity. For instance, the optical properties of noble metal2 and semiconductor3 NPs and the magnetic properties of ferrite NPs4 can be tailored by changing both their size and shape.

The cross-sections of NPs are typically orders of magnitude larger than those of organic molecules, and thus, absorption and scattering processes are key for certain applications.5 Metallic NPs are, for instance, much more efficient scatterers (>106-fold) than any organic molecule. Clearly, this has important implications in the context of biomedical applications, which are based on the response of materials to EM fields. Moreover, current synthetic bottom-up approaches allow for tailoring the interaction of NPs with a specific EM field by simply adjusting the composition, size, and shape.6,7 NPs can thus be engineered for a specific application. For example, NPs aimed at deep body imaging have to absorb and emit in the so-called biological window in the near-infrared (NIR), i.e., in the wavelength range of 800 to 1100 nm. Otherwise, both excitation and detection of the signal would be impaired due to scattering by the surrounding physiological components. For the case of noble metal NPs and quantum-dots (QDs), these optical features can be achieved by increasing the anisotropy of the NPs (e.g., nanorods, nanoprisms, nanostars, etc.)6 and by controlling the composition and diameter of the QDs,3 respectively. In the biological window, EM fields interact minimally with physiological components, such as blood, water, and fat.8 Quoting the words of Kotov: “the only way is up,” which makes reference to the tunability of the optical properties in the NIR of upconverting nanoparticles (UCNPs) for bioimaging.9

Bioimaging using shortwave infrared (SWIR) light with wavelengths from 0.9 to 1.7 microns represents another recent example in this direction. The recent development of indium gallium arsenide sensors has made SWIR imaging technically possible. Likewise, NIR and SWIR bioimaging benefit NPs, which can interact efficiently with these wavelengths.1011.12

In the following, some important parameters and relevant examples with regard to EM-active NPs will be discussed. The definitions of NPs and nanomaterials are relatively broad, and thus, to simplify, this review will focus on (1) colloidal NPs based on inorganic materials and (2) some relevant bioapplications with regard to the interaction of NPs with EM fields, i.e., bioapplications based on EM-active NPs. Please forgive me for the important omissions, as there will be plenty due to the wide scope of this topic. This review is intended for nonspecialists in any specific bioapplication of NPs. I hope it will provide an ample overview about the opportunities that EM-active NPs can offer in life science applications.

2.

Biological Performance by Chemical Design

Understanding the interplay between engineered NPs immersed in physiological environments and EM radiation is a complex issue that requires multidisciplinary teams in order to achieve relevant research developments. The best NPs in terms of physical properties might be useless for a specific bioapplication if they are toxic, unstable in physiological media, or covered by proteins nonspecifically,13 to mention just a few aspects. Nanotoxicology,14 functionalization of NPs with biomolecules,15 the protein corona,16 avoiding sequestration of NPs by the immune system,17 or using biocompatible EM fields,3 among others, are trending issues, which will surely determine the spread of bionanotechnology in the near future.

Two main aspects are critical toward the design of such functional NPs. First, the chemical design of the inorganic core needs to be optimized. The interaction between EM fields and NPs can be finely tailored by controlling NPs’ properties, such as size, shape, structure, and composition.3 While the inorganic material should act as an antenna, the fields should not affect the surrounding biological environment. EM-active NPs should also convert the absorbed or scattered EM fields into a specific response, such as fluorescence, field enhancement, nanoheating, etc. Second, the surface of these materials needs to be engineered to produce stable colloids in physiological media.13 That is, surface modifications are typically required to warrant long-term stability, prevent corrosion, preserve the original physical properties, etc. NPs can be further derivatized into biologically active NPs by surface modification with molecules of biological relevance, which confer additional features such as targeting capabilities, cell internalization features, prolonged circulation time, invisibility to the immune system, etc. The composition and thickness of the organic coating are also crucial as it forms the interphase between NPs and the environment, including ions, cells, proteins, tissue, etc.18 Please notice that the organic coatings might be intended (by design) or accidental, for example, due to the adsorption of proteins, which forms the so-called protein corona.16 Therefore, the coating may interfere with the NP’s response via thermal isolation, or quenching, enhancement or transfer of fluorescence, etc. One example in this direction is nanoheating by NPs. Theoretical calculations have shown that the heat produced by one single NP affects only the most immediate vicinity of the NP by thermal diffusion.19 Thus, as heat diffusion is confined within few nanometers from the NP’s surface, thick organic coatings will impede heating a target in the cellular membrane. Likewise, the protein corona has been reported as the prime target of such single NP heating, which may affect the biological fate of such a system in vivo.20 Not only nanoheating but also Raman and fluorescence signals can be affected by the physiological environment and, thereby, the bioperformance of NPs might be compromised. One has to keep in mind that the original design of the NPs can be severely affected by physiological components. Others and I have recently reviewed this topic in detail.13,16,18

3.

Biochemistry and Biomolecular Processes Occur at the Nano- and Microscale

In addition to the ability of NPs to interact efficiently with EM fields, the size scale where this interaction occurs is of utmost importance and suitability for biological processes. Being able to remotely manipulate nanomaterials with EM fields opens up a variety of opportunities in life sciences because biochemistry is actually governed by nano- and microscale processes, such as biomolecular recognition, molecular gradients, signaling pathways, cellular uptake, etc. The ability to control ion channels and neurons through heating of NPs is one remarkable example, which illustrates how EM-active NPs can control biological processes.21 Clearly, the size scale in this example is as important as the heating properties of the NPs, i.e., heating is required in the nanoscale only. The Gueroui group has reported other fascinating examples with regard to EM control over cellular fate by using functionalized magnetic NPs,2223.24 which were able to induce gradients of signaling proteins in the microscale by using magnetic field gradients.

EM-active NPs can be combined with one or more components from a library of molecules of biological relevance, including proteins, peptides, carbohydrates, nucleic acids, peptides, antifouling polymers, etc.25,26 The capability to perform more than one simple task is one of the most promising aspects of bionanotechnology, i.e., the so-called multifunctional NPs. The examples in the literature about multifunctional NPs are manifold,15,2728.29.30.31 and the combinations of molecules and NPs are very diverse. Figure 1 schematically depicts several possible functionalities, which are categorized depending on the NPs’ design. As previously acknowledged, this review focuses on EM-active NPs, and thus, several NP models and applications will not be discussed. This review will not cover NP models whose imaging, therapeutic, or sensing features are based on organic ligands/components, such as purely organic nanostructured materials, NPs as carriers of functional molecules, etc. As summarized in Table 1, three different categories of EM-active NPs will be considered, i.e., imaging, therapeutic, and biosensing agents.

Fig. 1

Schematic representation of three relevant types of active nanoparticles (NPs). The imaging panel represents three possible scenarios, i.e., photoemission, magnetic resonance contrast, and optoacoustic contrast, which can be realized by different types of NPs, including quantum-dots, magnetic NPs, and plasmonic nanomaterials (NMs). The heating panel represents the nanoheating capabilities of plasmonic and magnetic NPs, which upon coupling with light and radiofrequency (RF) radiation, respectively, are able to heat their surroundings, enabling hyperthermia and drug-release applications. The sensing panel depicts several biosensing applications driven by active NPs, such as colorimetric, Förster (fluorescence) resonant energy transfer, and SERS assays. The inner part of this figure (inside the dotted circle) represents the interaction between electromagnetic fields and NPs toward biological applications, whereas the outer part shows important molecules of biological relevance, which upon combination with different NPs (scaffolds) allows diverse range of multifunctionality.

JBO_19_10_101507_f001.png

Table 1

Electromagnetic (EM)-active nanoparticles (NPs) and corresponding applications.

ProcessNP modelsEM/NP interaction
ImagingPhotoluminescence (PL)Quantum-dots (QDs)32,33NPs absorb light of certain energy, which depends on the NPs’ model (size, shape, composition, etc.), and upon relaxation emit light.
Upconversion NPs (UCNPs)34
Metal nanoclusters (NCs)35
Optoacoustic (OI)Noble metal NPs36,37NPs absorb light, which typically is in resonance with the NPs’ plasmon band; the absorbed energy produces acoustic waves through thermoelastic expansion of the NPs.
Magnetic resonance (MRI)Magnetic NPs38NPs absorb radiation and produced alterations in magnetic relaxation of the surrounding atoms.
TherapyPlasmonic heatingNoble metal NPs,39 doped semiconductor NPs40NPs absorb light, which matches their plasmon band; the absorbed energy is transferred to the crystal lattice of the NPs, which upon relaxation get hot. Heating in the nanoscale occurs by thermal diffusion.
Magnetic heatingMagnetic NPs41The magnetic moment of magnetic NPs couples to alternating magnetic fields of radiofrequency radiation; upon magnetic reversal, the absorbed energy is dissipated in the form of heat.
PhotodynamicUCNPs42NPs absorb more than one photon, which triggers the emission of one photon at higher energy by anti-Stoke emission.
SensingOptical readoutNoble metal NPs43–45The optical, magnetic, or electric properties of NPs are affected by the detection of the analyte. In general, the NPs are modified with biomolecules, which can recognize a specific analyte. The actual change in these properties is related to the amount of analyte.
Magnetic readoutMagnetic NPs46
Electric readoutNoble metal, carbon nanotubes (CNTs)47,48

The range of functions provided to NPs by molecules can be as broad as the diversity of molecules. Therefore, and for the sake of simplicity, the molecules typically used to add biofunctionality(ies) to NPs could be categorized according to three main functions, i.e., targeting, antifouling, and treatment with drugs. Table 2 summarizes some of the most widely used molecules in combination with NPs.

Table 2

Molecules of biological relevance typically used in combination with NPs.

MoleculeFunctionExamples
TargetingAntibodiesLabeling of organelles and cellular components, sensingQDs49, magnetic NPs,50 metallic NPs45
CarbohydratesLectin-carbohydrate interactions, sensing, cellular uptakeQDs,51, metallic NPs52, magnetic NPs53
LipoproteinsCancer imaging and therapy,54 Alzheimer’s treatment55Polymeric NPs
HormonesTarget hormone-receptors in cancerAu NPs,56 CNTs57
FolateCancer imaging and therapyUCNPs,58 magnetic NPs,59 Au NPs60
AntifoulingPEGTo prevent unspecific interaction with plasma proteins, which ultimately leads to sequestration by the immune systemMetallic,61 magnetic,53 semiconductor,62 upconversion NPs63
Zwitterionic ligandsAu NPs,64 silica NPs65
DrugsNucleic acidsGene therapy, sensingMagnetic,66,67 Au NPs43,68–73
ChemotherapeuticsCancer treatmentMagnetic,74 Au,75 upconversion NPs,58 QDs28

In the literature, there are plenty of examples about multifunctional NPs designed to perform complex tasks simultaneously, using plasmonic,76 upconversion,77 semiconductor,78 or magnetic79 EM-active NPs as scaffolds upon which a diverse range of multifunctionality can be built. Furthermore, many NP models have been shown to work simultaneously as imaging and therapy agents, that is, multifunctional NPs typically referred to as theranostic probes. As we shall see in the following sections, NP models such as QDs, plasmonic, upconversion, and magnetic NPs can work as therapeutic and imaging agents. Although many of the most promising NP models have been shown to exhibit theranostic features, to simplify, this review will independently treat imaging and therapeutic NPs. Table 3 summarizes some examples of theranostic agents based on EM-active NPs.

Table 3

Theranostic EM-active NPs.

Imaging modalityTherapy modalityTargetingExamples
Magnetic NPsMRIHyperthermia/chemotherapyMagnetic fieldMagnetic polymersomes74
Radionuclide-based/ MRI/PLsiRNAHuman serum albumin coatingMultifunctional NPs80
PLsiRNAMagnetic fieldMagnetic lipospheres66
QDsPL/Förster (fluorescence) resonant energy transferChemotherapyAptamer-receptorMultifunctional QDs28
PLChemotherapy/ siRNAMultifunctional QDs81
UCNPsPLChemotherapyFolate-receptorsMultifunctional UCNPs58
PLsiRNA photo deliveryMultifunctional UCNPs82,83
PL/MRIPhotodynamicMultifunctional UCNPs84
Plasmonic NPsOptoacoustic/MRI/Dark-fieldDrug releaseAu nanoshells85
Optoacoustic/MRI/PLPhotoablationEnhance permeability and retention (EPR) effectGraphene oxide-magnetic NPs86
Computed tomographyRadiationEPR effectAu micelles87
Optoacoustic/dark-field/multiphoton/PLThermo-chemotherapyEPR effect/surface moleculesAu NPs, carbon nanomaterials, Pd nanosheets, Cu2−xSe88

4.

Nanoimaging

In this section, basic principles and opportunities with regard to the use of NPs as imaging nanoantennas will be discussed. Three main phenomena will be covered, that is, photoluminescence (PL), magnetic resonance imaging (MRI) contrast, and optoacoustic imaging (OI) contrast. Others also exist, such as thermal imaging,89,90 Raman mapping,91,92 x-ray computed tomography (CT),87 radionuclide-based imaging,80 or nonlinear optical phenomena, such as two-photon luminiscence;93 however, to date, they are less widely spread than the techniques covered herein. Please notice that this review focuses on imaging based on the physicochemical properties of the inorganic core of EM-active NPs and, therefore, imaging techniques based on NPs labeled with organic fluorophores or radio-labeled will not be discussed.

4.1.

Photoluminescence

Equivalent to common organic fluorophores, upon absorption of light, various NP models can emit light typically of longer wavelengths. Indeed, the colloidal synthesis of QDs was probably one of the main triggers of the current nanohype. These NPs made of semiconductor materials exhibit extraordinary fluorescence when they are illuminated at wavelengths intrinsically related to their composition, structure (core or core@shell), size, and surface chemistry.3 Actually, QDs present several enhanced optical features compared to organic fluorophores, such as size tunability of absorption and emission, high quantum yield, photostability, etc. For a detailed comparison between QDs and common dyes, the reader is referred to the work of Resch-Genger et al.5

Since the original works of Brus,94 Bawendy,95 Alivisatos,96 Weller et al.,97 and others,98,99 tremendous advances have been done with controlling the optoelectronic properties of QDs, that is, how QDs respond to light excitation. These have been achieved mainly by the steady developments in colloidal chemistry, which have enabled one to finely control the size, shape, composition, coating, etc., of QDs. Currently, synthetic methods permit us to choose QDs with almost any emission from the UV to the SWIR.100101.102.103 Yet, although QDs are very bright and photostable, their range of application in vivo has been traditionally limited due to toxicity concerns. Traditional QDs for in vivo imaging contain toxic ions, such as Cd, Hg, Te, Pb, etc., which can be released upon corrosion. Thus, less toxic compositions, such as InP/ZnS, Ag2S, or CuInS2/ZnS QDs, have been investigated as alternatives to provide new opportunities in the medical field.104 Coating methods have also been refined toward limiting the release of toxic ions, preserving the optical properties [high quantum yield (QY)], and enabling the colloidal stability of QDs in aqueous solution.105,106

Carbon nanomaterials, such as nanotubes, graphene, nanodots, and nanodiamonds, can also be used for bioimaging owing to their optical response.107,108 However, several aspects, such as cytotoxicity concerns, emission wavelength, or low extinction, which depend on the NP models, currently limit their use for bioimaging purposes.109

As an alternative to QDs, UCNPs represent a relatively new and exciting type of imaging agent. The upconversion phenomena involve the combined absorption of more than one photon, which triggers the emission of one photon at higher energy by anti-Stoke emission.9,110 UCNPs used for bioimaging are typically composed of a host matrix (e.g., Y2O3, Y2O2S, LaF3, NaYF4, and NaGdF4), doping lanthanide ions (e.g., Er3+, Tm3+, and Ho3+, which are the actual absorbers), and Yb3+ for enhancing the emission efficiency. Although the optical properties of UCNPs can be readily tailored by design, there is an important drawback with respect to QDs, that is, very low QY (0.005 to 0.3%).111 This point represents a challenging hurdle as it has a difficult solution due to the low extinction of the lanthanides.

Last in this section, a very new class of fluorescence probes is discussed, that is, fluorescence metal nanoclusters (NCs).112 NCs are made of few to hundreds of Ag and/or Au atoms (core size <2nm) capped with molecules, which also importantly affect their optical features.35 In contrast to bulk or NPs made of Au or Ag, the radiative decay of these NCs is very efficient. Indeed, the QY of NCs can be up to nine orders of magnitude larger than QY of the corresponding bulk material. NCs present good photostability in physiological media, high QY (although, in general, smaller than for QDs), broad tunability from the UV to the NIR, and large Stokes shifts.113,114 The opportunities that these materials open in the context of bioapplications are manifold; however, much work is still needed with regard to the impact of these materials on physiological environments. Au ions are toxic as Cd or Ag. However, Au NPs are believed to be among the safest NPs since they do not decompose readily because Au is the noblest metal. Clearly, in the case of Au NCs, which have an extreme surface-to-volume ratio, their corrosion behavior and cytotoxicity should be reevaluated. Understanding the biological fate and impact on proteins, organelles, etc., of NCs requires further investigations.

4.2.

MRI Contrast

MRI is widely used in the clinic and presents several advantages over other techniques, such as CT or positron emission tomography, which utilize ionizing radiation. MRI contrast is given by the distinct magnetic relaxation processes of the nuclear spins of hydrogen atoms in water and fat, the major hydrogen-containing components of the human body. Other elements can also be used, including He3, C13, F19, O17, Na23, P31, and Xe129. MRI is noninvasive, nondestructive, and allows for full-body three-dimensional reconstruction with high spatial resolution and excellent soft tissue contrast.4 Nevertheless, MRI as an endogenous technique suffers from poor sensitivity. Therefore, contrast agents, such as gadolinium-complexes and iron oxide NPs, are widely used, enabling superior sensitivity. It should be noted that gadolinium-complexes might release toxic ions and suffer from low circulation time.4 Iron oxide NPs are actually used to induce local field inhomogeneities (as nanoantennas) that affect the relaxation time of protons, leading to positive or negative contrast. Indeed, tailoring the size of these NPs from <4nm to ca. 40 nm can be used to produce distinct effects on the relaxivity, called longitudinal or T1, and transversal or T2. Furthermore, doping with transition metal ions or clustering of NPs induces very high contrast (in this case via enhancement of T2). The tunability, biocompatibility, and versatility make iron oxide NPs, in terms of biofunctionalization, a promising candidate for being widely used in the clinic. We refer to the original work of Lee and Hyeon for an extended review of this topic.4

4.3.

Optoacoustic Imaging

The newest and most exciting technique is discussed last in the imaging section, owing to the simplicity of its principles and the fact that it is based on already developed technologies, i.e., sonography and tomography.115 OI is a hybrid technique that listens to light. The principle relies on detecting acoustic waves upon thermal relaxation of a photoabsorber excited with an intense pulse of NIR light, cf. Fig. 2. The two main advantages are the penetration depth, owing to NIR excitation, and the fact that resolution is not affected by scattering, as it is based on ultrasound. However, sensitivity can be poor due to limited endogenous contrast. Thus, NPs are ideal probes as OI contrast agents, with improved sensitivity, optical tunability by chemical design, and biotargeting capabilities. To date, carbon nanotubes (CNTs) and anisotropic metal nanoparticles (Au and Ag) have been tested as OI contrast agents with excellent results in vivo.36,37,116117.118 The main requirement of these probes is that they should be able to absorb in the NIR; clearly, materials with highest absorption will produce best contrast.119 Current synthetic methods can be used to synthesize NPs with absorption bands in the range where OI operates. For instance, gold nanoprisms and nanorods,37,120 whose plasmon band can be adjusted along the NIR by chemical design, have been used as OI contrast agents. Actually, expanding the excitation sources used by OI into the SWIR will improve the possibilities of this technique owing to deeper tissue penetration.3,121

Fig. 2

(a) Schematics of an optoacoustic imaging (OI) system. The slight fiber bundle angle allows illumination of the sample exactly above the transducer array. The animal holder allows the sample to be moved and the recording of sequential slices in precise and predefined steps. (b) OI system used in the work of Bao et al., which reported the OI bioimaging of gastrointestinal cancer by using gold nanoprisms.37 The clear illumination ring on the animal, which is wrapped in a thin transparent plastic foil and placed in a water tank, allows homogeneous light energy to be transferred around the focal point of the transducer array. Reproduced with permission from Ref. 37.

JBO_19_10_101507_f002.png

As summary of the imaging section, Table 4 shows important parameters for the different imaging modalities and selected EM-active NP models.

Table 4

Imaging using EM-active NPs.

Imaging modalityNPs modelExamplesTuning parametersProsCons
PLQDsAg2S (QY: 15.5%)12Size, shape, surface chemistry, structure3Fast (<200  ms per frame)125 Sensitivity: picomolarSpatial resolution (SR: 1 to 3 mm; one recent work ∼30  μm)125 Tissue penetration (<1  cm)
CuInS2/ZnS (QY: 20 to 30%)102
C-dots (QY: 17%)122
Nanodiamonds (QY: 70%)123
Si NPs (QY: 60%)124
UCNPsNaYF4: 2% Er3+, 20% Yb3+ (QY:0.005 to 0.3%)111Doping, size126
NCsAu NCs (QY: 2.9%)Size, ligands, doping127
Au/Ag NCs (QY: 3.4%)
AgxAu25−x (x=1 to 13) (QY:40.1%)127
MRIT2 agents (superparamagnetic and ferrimagnetic NPs)Fe3O4, MnFe2O4, (ZnxMn1−x)Fe2O4, Fe/MnFe2O4 NPs4Size, doping, structure, ligands4SR: ∼50  μm Unlimited tissue penetrationSensitivity: micromolar to nanomolar Slow processing
T1 agents (superparamagnetic and paramagnetic NPs)Ultrasmall Fe3O4,128Mn3O4,129Gd2O3 NPs38
OIMetal NPs, carbon nanomaterialsAu nanorods,36 Au nanoprisms,37 Au nanocages,117 Ag nanoprisms,118 graphene nanosheets,86 CNTs116Size, anisotropy, structure119SR: ∼50  μm Sensitivity: picomolar FastTissue penetration (<5  cm) Still developing

QY, quantum yield.

5.

Nanotherapy

Most of the therapeutic uses of NPs, i.e., nanomedicine, are based on loading the NPs with a variety of functional molecules, thereby enabling multifunctional NPs.68,130 Cancer treatment has been one major area where NPs have been extensively applied.131 Ideally, multifunctional NPs should circulate in the bloodstream undetected by the immune system, reach the targeted region, and release or expose a drug or stimuli. Multifunctional NPs present not only several advantages compared to common therapeutic drugs, such as prolonged circulation time, targeting capabilities, superior stability, and enhanced pharmacokinetics, but also potential theranostic features. The diversity of therapeutic NPs can be as broad as the potential drug molecules that can be loaded on the NPs, including anticancer drugs, proteins, and nucleic acids.132 Although the therapeutic opportunities of NPs are manifold, this review focuses on EM-active NPs alone, and thus, two main therapeutic processes will be discussed: nanoheating and photodynamic therapy (PDT). The therapeutic gain relies on the interaction of the inorganic core of NPs with EM fields. Although other NP-based therapeutic approaches exist, nanoheating and PDT are among the most widely investigated.

A variety of nanomaterials show great promise as nanoheaters, that is, NPs able to produce heat locally (at its surroundings) upon EM irradiation. In many applications based, for example, on plasmonics or in MRI, nanoheating is actually an unwanted phenomenon.133 Several bioapplications based on nanoheating using NPs have been mainly developed in the last decade. Applications such as negative index of refraction, focusing and imaging with subwavelength resolution, invisibility cloaks, etc., require low-loss plasmonic materials, i.e., graphene, alkali metals, etc., as alternatives to noble metals, such as Au and Ag, which are indeed excellent for nanoheating.133

The capability of being able to release heat upon remote EM exposure has opened new opportunities for a variety of goals in life sciences. Local heating with colloidal NPs has been used for killing tumoral cells,134 drug-release applications,135,136 ultralow detection of tumoral markers,45 imaging in vivo37 and in vitro,137 or even sterilization.138 In the frame of oncological hyperthermia, both magnetic and plasmonic NPs have been investigated as nanoheaters. Either can be remotely activated by radiation that do not or minimally interact with physiological tissues and fluids. Actually, the major challenge concerning colloidal chemistry within this framework resides in being able to produce NPs that absorb in EM regions where tissue absorption remains minimum, i.e., biological windows. Engineered nanomaterials with tailored heating performance, as well as suitable organic coatings, are continuously developed toward more efficient interactions with EM radiation and the performance of more complex tasks in biological environments. As previously discussed, these materials can be used simultaneously as contrast agents by using imaging techniques that rely on their magnetic (e.g., MRI) or plasmonic behavior (e.g., OI), thereby enabling theranostic NPs. Moreover, plasmonic nanoheating can be used in combination with other therapeutic and imaging approaches. Chen, Nie, and coworkers have recently reported on plasmonic nanoheating combined with PDT.63 They proposed a theranostic nanoplatform based on plasmonic photosensitize-loaded vesicles, which, in addition, can be used as triple-imaging agents, i.e., NIR fluorescence, thermal and photoacoustic imaging, cf. Fig. 3. Previous works have demonstrated the feasibility of dual imaging-therapeutic NPs based on active NPs by using magnetic and resonant light excitation.139,140

Fig. 3

Theranostic NPs: photosensitizer (Ce6)-loaded plasmonic gold vesicles, which provide trimodal imaging capabilities, i.e., fluorescence, thermal and OI, and photothermal/photodynamic cancer therapy. Reproduced with permission from Ref. 63.

JBO_19_10_101507_f003.png

Two main decay processes (heat losses) can be accountable for nanoheating, i.e., magnetic relaxation and plasmonic relaxation. Both are based on the capability of magnetic and plasmonic NPs to couple to the magnetic component of radiofrequency (RF) radiation or the electric component of light, respectively. Thus, local heating can be produced upon dissipation of the absorbed energy.

5.1.

Plasmonic Heating

Most relevant plasmonic NPs for nanoheating include noble metals [Au (Ref. 134) and Ag (Ref. 141), semiconductor NPs [Cu2xSe,40 CuS,142 and CuTe (Ref. 143)], CNTs,139 and graphene nanomaterials.144 The variety of compositions, sizes (from 10 nm to hundreds of nanometers), and shapes (core-shell, rod-like, cube, star-like, prismatic, triangular, etc.) is remarkable. Their common property is NIR activity. As previously discussed, ideal plasmonic nanoheaters should absorb as much light as possible and they should also exhibit high heating losses (high conductivity). Thus, Au represents an ideal nanoheater, in principle safer than Ag due to toxicity concerns. Ag NPs are more readily oxidized than Au, releasing toxic Ag ions. Therefore, most up-to-date plasmonic nanoheating studies have been carried out with Au anisotropic NPs, such as nanorods134 or nanoprims39, and gold nanoshells.145

The light-to-heat mechanism involves the resonant absorption of light by the conduction electrons of the NPs, which couple to the incoming radiation. Scattering between the hot electrons and the crystal lattice enables energy dissipation by phonon-phonon scattering. For details about the plasmonic photothermal effect, the reader is referred to an excellent review by Baffou and Quidant, which discusses many important parameters, including thermal diffusion, continuous or pulse illumination, coupling effects, and thermal confinement, among others.19

Plasmonic nanoheating therapy has been explored using different approaches, ablation of tumoral cells being the most straightforward and widely reported to date.146,147 The use of plasmonic nanoheating for cancer treatment has indeed reached clinical trials (see AuroLase® Therapy). The principle is simple, as it only requires surface modification of the nanoprobes to enable cellular uptake and prolonged circulation time, and a light source. Different biofunctionalization strategies using biomolecules have been reported to date, enabling specific targeting. Though simple, this approach is very powerful, due to the spatiotemporal control of the illumination of the tissue’s areas to be destroyed.

Other more elegant approaches employ nanoheating to promote drug release, which can then be used for killing or treating the targeted cells. Halas and coworkers used the nanoheating-release approach by using nanorods and nanoshells.136,148149.150 In one particularly interesting example, they functionalized the nanoheaters with complementary nucleic acid strands, which upon light excitation can undergo dehybridization of the complementary strand, i.e., the therapeutic drug siRNA, inducing gene silencing.136 Other approaches have been employed in organic microparticles (layer-by-layer capsules,151 liposomes,152 polymer particles,75 etc.) functionalized with plasmonic NPs, which upon illumination can undergo a phase transition, enabling the release of the caged drug inside the cells. Parak and coworkers have used plasmonic polyelectrolyte capsules to release different drugs, including polymers,153 pH indicators, and proteins,154 as well as nucleic acids,67 inside the cytosol of cells at the level of single cells.

5.2.

Magnetic Heating

Another type of nanoheaters involves the coupling of the alternating magnetic field of radio-frequency radiation to the magnetic moment of magnetic NPs. Magnetic dipoles result from the spinning of some of the NP electrons. These polarized electrons can align parallel or antiparallel with respect to the neighboring ones and respond very differently to an applied magnetic field. This, in turn, defines how materials are classified as paramagnets, ferromagnets, ferrimagnets, or antiferromagnets. Falling into one of these categories depends on the size of the material, and thus, the magnetic behavior of a particular material can be tuned by adjusting its size.155 Indeed, superparamagnetism is intrinsically linked to the nanometer range. In contrast to ferromagnetic and ferrimagnetic (FM) NPs, in the absence of a magnetic field, superparamagnetic (SPM) NPs are not magnetized. This actually prevents magnetic coupling and, subsequently, unwanted agglomeration of NPs. Obviously, magnetic agglomeration should be prevented to preserve the colloidal stability and properties of the materials. This is especially important for biological applications where agglomeration can impede the performance of the nanomaterial. Furthermore, the magnetic dipole of SPM NPs and single-domain small FM NPs can couple to RF radiation using relative low field amplitudes, which enables the heating of their local environment upon energy dissipation. This is the basis of magnetic fluid hyperthermia, a technique investigated for decades in the field of cancer treatment.156157.158.159.160 The pillars of this therapeutical technique are (1) tumors are inherently more susceptible to increased temperatures than healthy tissue; (2) magnetic NPs can produce heat upon excitation with RF radiation; and (3) the intensity and energy required for exciting these NPs is in a physiological regime, which typically requires frequencies and field amplitudes <1MHz and 250 G, respectively. Tissue surrounding tumors and nontargeted with NPs will not be damaged upon RF exposure.

Many of the research efforts concerning magnetic hyperthermia have been devoted to the development of NPs with the highest specific absorption rate (SAR), i.e., the capability of the magnetic fluids to absorb and heat as much as possible. There are different models that aim to explain magnetic relaxation processes involved in magnetic heating. Ultimately, the source of nanoheating is the magnetic reversal of the magnetic moment of a single NP.161 Magnetic reversal is actually influenced by several properties, such as magnetic anisotropy, size, shape, composition, and coupling effects, which ought to be synthetically tailored for specific RF excitations. Traditionally, iron oxide NPs (magnetite and/or maghemite) with diameters <15nm have been used for magnetic fluid hyperthermia. The company MagForce AG (Berlin, Germany) utilizes ca. 15-nm iron oxide cores with an aminosilane coating in clinical trials. However, SAR of these NPs is extremely low and, therefore, large doses are required for achieving hyperthermic temperatures in tumors. Employing NPs with optimized SAR values can substantially reduce the required doses, and therefore, many recent works have focused on the development of more efficient magnetic nanoheaters, such as exchange-coupled magnetic NPs (e.g., CoFe2O4@MnFe2O4),7 iron oxide nanocubes,162,163 iron NPs,164 and iron carbide NPs.165 Interestingly, magnetosomes produced by magnetotactic bacterium have been reported to produce unusually large SAR values compared to similar magnetic NPs produced by synthetic colloidal methods.166,167 This indeed indicates that there is still space for improving synthetic methods to produce more efficient materials.

As was the case for plasmonic heating, most of the reports on magnetic nanoheating involve the destruction of tissue by heating.168,169 Many efforts have been devoted to achieving active targeted therapy by functionalization with specific targeting ligands or by using specific cells as Trojan horses.41,170,171 Figure 4 shows a classical example of magnetic hyperthermia in which clusters of iron oxide NPs—functionalized with folic acid and polyethylene glycol (PEG) to enhance tumor accumulation—act as nanoheaters and MRI contrast agents.41 Nevertheless, the most widely used phenomenon toward targeting tumors makes profit of a passive response, i.e., enhanced permeability and retention effect, by which particles typically >100nm are retained inside tumors due to their characteristic vascularity.172 Yet, although to a lesser extent than plasmonic heating, other works have attempted to use magnetic heating as a route to promote drug release,173 or even targeting of specific cellular receptors, which can be altered by magnetic nanoheating.21,174 Figure 5 shows one interesting example of RF-driven smart release.175 In this work, Aoyagi and coworkers reported a smart hyperthermia nanofiber, which combines heat generation and drug release to induce skin cancer apoptosis.

Fig. 4

(a) Photograph (left) and thermal image (right) of a mouse 24 h after intravenous injection of iron oxide agglomerates functionalized with PEG and folic acid [folic acid-polyethylene glycol functionalized superparamagnetic iron oxide nanoparticles (FA-PEG-SPION) nanoclusters (NCs)] under an ac magnetic field with H=8kA/m and f=230kHz. (b) Tumor-growth behavior and (c) survival period of mice without treatment and treated by intravenous injection of FA-PEG-SPION NCs, application of an ac magnetic field, and application of an ac magnetic field 24 h after intravenous injection of FA-PEG-SPION NCs (n=5). (d) Photographs of mice 35 days after treatment. Reproduced with permission from Ref. 41.

JBO_19_10_101507_f004.png

Fig. 5

Design concept for a smart hyperthermia nanofiber system that utilizes magnetic NPs (MNPs) dispersed in temperature-responsive polymers. Anticancer drug doxorubicin (DOX) is also incorporated into the nanofibers. The nanofibers are chemically crosslinked. First, the device signal (AMF) is turned on to activate the MNPs in the nanofibers. Then, the MNPs generate heat to collapse the polymer networks in the nanofiber, allowing the “on-off” release of DOX. Both the generated heat and released DOX induce apoptosis of cancer cells by hyperthermic and chemotherapeutic effects, respectively. Reproduced with permission from Ref. 175.

JBO_19_10_101507_f005.png

5.3.

Photodynamic Therapy

PDT has been investigated to treat cancers for >100 years.176 The therapeutic action of PDT relies on the excitation of photosensitizers by light in the presence of oxygen, which enables the production of singlet oxygen in the illuminated areas and, thus, the killing of treated cells. As for plasmonic nanoheating, its therapeutic power resides in the use of light as stimulating triggers for a great degree of spatiotemporal control. Several photosensitizers have been developed,177 even activatable photosensitizers that require molecular activation, such as quenching, pH, solvent, or hydrophobicity.178 Also, some hybrid materials that combine photosensitizers and NPs have been described.179180.181.182 In all the above examples, PDT is achieved by direct light excitation of photosensitizers, which may be or may not be tagged on passive NPs, cf. Fig. 3.63,183 This review will focus on PDT by EM-active NPs in which reactive oxygen species (ROS) is directly produced by illumination of NPs or by activation of photosensitizers through illumination of NPs.

TiO2 NPs, a widely used material in consumer products,184 have been shown to produce ROS upon UV illumination.185,186 However, the use of UV light in cytotoxicity studies is rather challenging due to the intrinsic toxicity of UV light. To overcome this, the doping of TiO2 NPs with different elements has been explored for allowing the TiO2 NPs’ photocatalytic properties into the visible.187,188 To date, light activation of TiO2 NPs represents a major safety concern for nanotoxicology rather than a therapeutic opportunity,185 although some reports exist.189190.191

Equivalent to common photosensitizers, QDs have also been proposed as intrinsic PDT agents.192193.194 However, the QYs of the singlet oxygen of QDs are very low compared to the ones of common photosensitizers (ca. 1 to 5% versus 20 to 30%). Therefore, most of the reports regarding PDT and QDs describe the use of common photosensitizers in combination with QDs.195196.197 Upon light absorption, photosensitizer-derivatized QDs can produce singlet oxygen. In this case, QDs act as an intermediate of the activation, also known as Förster (fluorescence) resonant energy transfer (FRET) donor. By both one- or two-photon absorption, QDs can be excited with the appropriate light source, and they can subsequently activate photosensitizers, which absorb in the UV-visible. Please notice that the use of PDT has been traditionally limited to surface tumors because usual photosensitizers require low-penetration UV-visible light. Two-photon NIR excitation of photosensitizer-loaded QDs would be highly beneficial for PDT in vivo.198 Both mechanisms, i.e., FRET-based or direct activation of QDs, result in the generation of reactive singlet oxygen species that can be used for PDT cancer therapy.

On the other hand, the combination of UCNPs and photosensitizers shows great feasibility for cancer treatment, as reported by several works.42,77,199200.201.202 UCNPs have been widely used as FRET donors in PDT, which can be activated by NIR light. Photosensitizers are typically embedded in the silica coating of UCNPs, which can undergo energy transfer to the photosensitizers upon NIR excitation, thereby enabling the production of singlet oxygen. Indeed, the unique NIR features of UCNPs make them the ideal platform for PDT. UCNPs solve two of the most important limitations of photosensitizers, i.e., low solubility in aqueous solution and UV-visible activity. Several reports have shown the feasibility of using UCNPs as NIR transducers in PDT in vivo.42,77,199 The interested reader is referred to the recent work of Arguinzoniz et al., which has covered in detail the most important aspects of PDT driven by NPs.177

To finish this section, I would like to emphasize that there are many other NP models, EM-active or passive, which can be used for therapeutic purposes though they remain less explored to date. Other therapeutic approaches can also be achieved with the NP models discussed so far. In addition to PDT, for instance, the upconversion phenomenon can be used for NIR-driven release of photocaged compounds.34,82 The most common role of NPs in therapy is as drug carriers,203 which has not been discussed in this review because the therapeutic function of NPs does not rely on the interaction with fields in most of the cases. Therapeutic agents with low solubility (e.g., chemotherapeutic drugs74 or photosensitizers204) and/or susceptible to quick degradation (e.g., nucleic acids68) can be loaded into NPs with high yield and in combination with other molecules.

6.

Nanobiosensing

The capability of EM-active NPs to act as biosensors relies on changes of their physical properties upon analyte recognition, which can be detected by means of a quantifiable optical, thermal, electric, or magnetic signal. Herein, some sound examples of biosensing using EM-active NPs will be discussed. Biosensing using NPs for mass amplification of the signal upon recognition will not be discussed, i.e., microcantilevers or quartz crystal microbalance technology, as in this case, the role of NPs is passive, meaning not active in terms of interaction with fields.

6.1.

Optical Readout

The most straightforward and widely used biosensor based on active NPs relies on a change of color (energy resonance), i.e., colorimetric sensors. These have been used to detect the presence of an analyte by simple visual inspection (yes or no sensor), or by spectroscopic means (e.g., plasmon resonance and surface-enhanced Raman). Au and Ag NPs display absorption band(s) in the visible range, which makes them very suitable probes for visual inspection. The plasmon band is mainly determined by the composition, size, and shape of the NPs.2 However, changes in the dielectric environment also affect the resonance. This is the basis of localized surface plasmon resonance (LSPR) sensing based on LSPR shifts, where metallic NPs anchored to a substrate produce an LSPR shift upon analyte detection. The most suitable probes are those more sensitive to dielectric changes, such as gold nanorods.205 This technique can be used to detect almost any analyte as long as the colloids are derivatized with catching biomolecules, such as nucleic acids,206 antibodies,207208.209 carbohydrates,210 etc. Figure 6 shows a schematic representation of the basic process of agglomeration, which is caused by the recognition of analytes, and its detection by LSPR.211 The interested reader in refractometric nanoplasmonic biosensors is referred to two recent reviews from the group of Lechuga.212,213

Fig. 6

(a) Schematic representation of the basic process of the analyte-driven agglomeration reaction. Au NPs functionalized with oligonucleotide sequences (Oligo-AuNP conjugates 1 and 2) are bound together into a large agglomerate network by the target sequence 1′2′. (b) Schematic of the principles of the side illumination waveguide system used to illuminate the scattering of the samples. (c) Photograph of representative samples on the side illumination system showing the visible red shift of agglomerated versus monodispersed Au NPs. (d) This shift can also be observed in the localized surface plasmon resonance spectroscopy of the samples. Reproduced with permission from Ref. 211.

JBO_19_10_101507_f006.png

Yet though LSPR sensing is very versatile, colloidal agglomeration as a colorimetric sensor is extremely sensitive and straightforward, allowing for even naked eye detection. The group of Mirkin has reported pioneering works regarding colorimetric biosensors based on DNA-modified Au NPs.43,6970.71.72.73,214 The original work describing this concept reports on NP agglomeration (color change) driven by detection of DNA sequences complementary to two DNA-modified Au NPs.215 Since this pioneering work, the group of Mirkin has extensively explored the use of ligand-modified Au NPs for biosensing applications. Figure 7 shows one example, which illustrates the versatility and power of this sensing approach, where biobarcoded NPs were used for multiplexed detection of protein cancer markers.43

Fig. 7

Biobarcode assay for multiplexed protein detection. Reproduced with permission from Ref. 43.

JBO_19_10_101507_f007.png

This type of assays has developed into more complex assays, such as colorimetric logic gates.216,217 The strength of colorimetric assays relies on the sensitivity of surface plasmons when there is coupling between plasmonic colloids. For instance, dimers of Au NPs (20 nm) with interparticle distances of <10nm will have a significant impact on the plasmon resonances, both in the cross-section and wavelength.6

Another type of optical biosensors is based on FRET. The process requires donor-acceptor pairs in close proximity (1 to 10 nm). Au NPs and QDs have been extensively used in FRET bioassays, the former as donors, which can quench fluorescence of an acceptor due to their high extinction coefficients.218 In this way, several different approaches can be used to recover fluorescence upon analyte binding, for example, by using a competitive fluorescence molecule (quenched on the surface of the NP) whereby release occurs (fluorescence recovered) upon analyte detection.219 Likewise, plasmonic NPs can be used to enhance the fluorescence of dye molecules placed at ca. 10 nm from the NPs’ surface.220 Actually, fluorescence quenching or enhancement depends on the distance between the NPs and the dye.221 In a recent elegant work on DNA-directed nanoantennas, 117-fold fluorescence enhancement was observed for a dye molecule positioned in the 23-nm gap between 100-nm gold NPs.222

In contrast to Au NPs, QDs are typically employed as energy donor molecules in FRET assays. The tunability of QD emission wavelength, large Stokes shifts, and wide absorption spectra enables them to be used as multiplexing agents.223224.225 As in the case of Au NPs, QDs can be functionalized with biomolecules, which allow for competitive assays or simply analyte recognition whereby the fluorescence is “switch on/off”.226

Next in this section, basic principles and some examples regarding surface-enhanced Raman scattering (SERS) biosensing are discussed. However, for details about the opportunities and challenges that this ultrasensitive technique can offer, the reader is referred to a recent work of Alvarez-Puebla and coworkers.227228.229.230 Briefly, SERS sensing is based on a strong enhancement of the Raman signals upon analyte detection by plasmonic NPs (typically Au and Ag NPs). In principle, this technique can detect single molecules.231 The Raman signal depends strongly on the distance of the Raman reporter to the surface of the NPs, quickly extinguishing as the reporter moves away from the surface. Larger enhancements occur in the gap within agglomerates of NPs, allowing for ultrasensitive sensing. Obviously, between 1- and 2-nm gaps, the range of biomolecules that can fit is very limited. SERS-encoded NPs have been used for multiplex imaging in vivo,44,232 which could be used for detection of multiple biomarkers associated with a specific disease. The company Oxonica Materials commercializes highly versatile signal-reliable SERS-encoded NPs. These consist of silica-coated agglomerates of Au NPs, which can be encoded with different SERS tags.

As an alternative to agglomerates, many investigations have been focused on developing synthetic methods to produce anisotropic plasmonic NPs with sharp apexes (nanostars, nanorods, nanoprims, etc.), which can have hot-spots that concentrate large field enhancements.233 By synthetic design, anisotropic plasmonic NPs can be used for energy concentration at the nanoscale. This is actually a fascinating property of plasmonics using EM-active NPs, with many applications besides SERS sensing.228 Controlled assemblies of plasmonic NPs have been reported to improve SERS sensitivity, whether it is formed by few NPs234 or by two-dimensional self-assemblies in large supports.235

Last, photothermal biosensing is briefly introduced. Though the signal is, in this case, thermal, this is achieved due to photoheating using plasmonic NPs. The principle is simple, that is, plasmonic NPs are functionalized with catching biomolecules, which upon recognition immobilize the plasmonic complex in a support. Then, light excitation can produce a thermal signal, which can be detected by simple visual inspection on a thermosensitive support or by a thermal camera.236 The sensitivity, which can be up to attomolar range in serum of patients,45 and the simplicity of this method are astonishing. The principles and protocol of this novel approach are schematically represented in Fig. 8, for the case of detection of a common cancer marker, i.e., carcinoembryonic antigen.45

Fig. 8

Schematic representation of thermal biosensing. Step-by-step processes for the formation of the immunocomplex using anti-carcinoembryonic antigen derivatized nanoprism (NPRs), enabling thermal sensing upon near-infrared illumination. Reproduced with permission from Ref. 45.

JBO_19_10_101507_f008.png

6.2.

Magnetic Readout

As in the case of colorimetric biosensors, magnetic NPs can be driven to agglomeration upon analyte recognition, which, in this case, will affect the magnetic relaxation of the surrounding proton spins (as in MRI). As previously mentioned, tailoring the magnetic properties of NPs and, thus, their interaction with RF radiation can be achieved by adjusting the size, shape, and composition of the NPs. This principle can be used to investigate biomolecular interactions, such as DNA-DNA, protein-protein, protein-small molecule, and enzyme reactions.46 Importantly, though these measurements require magnetic resonance equipment, which is an obvious disadvantage compared to colorimetric visual inspection, they can be carried out in dirty environments, meaning that sample pretreatment, such as purification, is not required.

6.3.

Electric Readout

The electrical detection of target analytes by EM-active NPs, such as CNTs or Au NPs, is based on the measurement of their conductivity and impedance properties upon target recognition. Indeed, CNTs and Au NPs have been widely used as transducers in potentiometric analysis.236237.238 As in the different sensing methods discussed so far, the most important concept here is that NPs are functionalized with catching molecules, which, upon recognition, change the properties of the transducers. For instance, an aptamer-based CNT potentiometric sensor has been used to detect ultralow concentrations of bacteria.48

Another type of electrical sensors is based on the photochemistry of QDs whereby charge carriers can be injected into redox reactions upon light excitation. Thus, current changes depend on whether a reaction occurs, in a quantitative manner, and upon light excitation, which allows one to investigate spatiotemporal-driven reactions.47,239,240

7.

Conclusions and Outlook

The applications of NPs in life science are growing dramatically. As the control over the synthesis of complex NPs evolves, new applications and opportunities can be explored. Two main concepts are to be highlighted: first, EM radiation can be absorbed by inorganic NPs, enabling many highly useful responses, like photoluminescence, nanoheating, magnetic coupling, etc. Second, hybrid NPs composed of inorganic EM-active cores and molecules of biological relevance are required for bioperformance enhancement.

Though the field of nanobiotechnology is now in the forefront of science, there are still fundamental issues that have to be deeply addressed, such as the impact of NPs on life, including biocompatibility, toxicity, ecotoxicity, etc.; in vivo targeting of specific diseases, markers, etc.; prevention of the unspecific interaction with proteins and accumulation in liver and spleen; and understanding of energy relaxation on NPs and related topics, like hot electrons, magnetic relaxation, heat diffusion in the nanoscale, etc., to mention just few. More work is needed on the development of multifunctional-theranostic NPs, which can perform more than one simple task or serve for more than a proof of principle. As many proof of principles are already established in this area, more efforts should be put into achieving real medical solutions.

References

1. T. K. Sauet al., “Properties and applications of colloidal nonspherical noble metal nanoparticles,” Adv. Mater. 22(16), 1805–1825 (2010).ADVMEW0935-9648 http://dx.doi.org/10.1002/adma.v22:16 Google Scholar

2. L. M. Liz-Marzan, “Tailoring surface plasmons through the morphology and assembly of metal nanoparticles,” Langmuir 22(1), 32–41 (2006).LANGD50743-7463 http://dx.doi.org/10.1021/la0513353 Google Scholar

3. A. M. SmithS. Nie, “Semiconductor nanocrystals: structure, properties, and band gap engineering,” Acc. Chem. Res. 43(2), 190–200 (2010).ACHRE40001-4842 http://dx.doi.org/10.1021/ar9001069 Google Scholar

4. N. LeeT. Hyeon, “Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents,” Chem. Soc. Rev. 41(7), 2575–2589 (2012).CSRVBR0306-0012 http://dx.doi.org/10.1039/c1cs15248c Google Scholar

5. U. Resch-Gengeret al., “Quantum dots versus organic dyes as fluorescent labels,” Nat. Methods 5(9), 763–775 (2008).1548-7091 http://dx.doi.org/10.1038/nmeth.1248 Google Scholar

6. V. Myroshnychenkoet al., “Modelling the optical response of gold nanoparticles,” Chem. Soc. Rev. 37(9), 1792–1805 (2008).CSRVBR0306-0012 http://dx.doi.org/10.1039/b711486a Google Scholar

7. J.-H. Leeet al., “Exchange-coupled magnetic nanoparticles for efficient heat induction,” Nat. Nanotechnol. 6(7), 418–422 (2011).1748-3387 http://dx.doi.org/10.1038/nnano.2011.95 Google Scholar

8. A. M. Smithet al., “Bioimaging: second window for in vivo imaging,” Nat. Nanotechnol. 4(11), 710–711 (2009).1748-3387 http://dx.doi.org/10.1038/nnano.2009.326 Google Scholar

9. N. Kotov, “Bioimaging: the only way is up,” Nat. Mater. 10(12), 903–904 (2011).NMAACR1476-1122 http://dx.doi.org/10.1038/nmat3181 Google Scholar

10. J. K. Streitet al., “Directly measured optical absorption cross sections for structure-selected single-walled carbon nanotubes,” Nano Lett. 14(3), 1530–1536 (2014).NALEFD1530-6984 http://dx.doi.org/10.1021/nl404791y Google Scholar

11. Y. Duet al., “Near-infrared photoluminescent Ag2S quantum dots from a single source precursor,” J. Am. Chem. Soc. 132(5), 1470–1471 (2010).JACSAT0002-7863 http://dx.doi.org/10.1021/ja909490r Google Scholar

12. G. Honget al., “In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region,” Angew. Chem. Int. Ed. 51(39), 9818–9821 (2012).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.201206059 Google Scholar

13. B. Pelazet al., “Interfacing engineered nanoparticles with biological systems: anticipating adverse nano-bio interactions,” Small 9(9–10), 1573–1584 (2013).1613-6829 http://dx.doi.org/10.1002/smll.201201229 Google Scholar

14. P. Rivera-Gilet al., “Correlating physico-chemical with toxicological properties of nanoparticles: the present and the future,” ACS Nano 4(10), 5527–5531 (2010).1936-0851 http://dx.doi.org/10.1021/nn1025687 Google Scholar

15. D.-E. Leeet al., “Multifunctional nanoparticles for multimodal imaging and theragnosis,” Chem. Soc. Rev. 41(7), 2656–2672 (2012).CSRVBR0306-0012 http://dx.doi.org/10.1039/c2cs15261d Google Scholar

16. P. d. Pinoet al., “Protein corona formation around nanoparticles—from the past to the future,” Mater. Horiz. 1, 301–313 (2014).MHAOBM2051-6355 http://dx.doi.org/10.1039/C3MH00106G Google Scholar

17. P. P. KarmaliD. Simberg, “Interactions of nanoparticles with plasma proteins: implication on clearance and toxicity of drug delivery systems,” Expert Opin. Drug Deliv. 8(3), 343–357 (2011).1742-5247 http://dx.doi.org/10.1517/17425247.2011.554818 Google Scholar

18. P. Rivera-Gilet al., “The challenge to relate the physicochemical properties of colloidal nanoparticles to their cytotoxicity,” Acc. Chem. Res. 46(3), 743–749 (2013).ACHRE40001-4842 http://dx.doi.org/10.1021/ar300039j Google Scholar

19. G. BaffouR. Quidant, “Thermo-plasmonics: using metallic nanostructures as nano-sources of heat,” Laser Photon. Rev. 7(2), 171–187 (2013).1863-8880 http://dx.doi.org/10.1002/lpor.2013.7.issue-2 Google Scholar

20. M. Mahmoudiet al., “Variation of protein corona composition of gold nanoparticles following plasmonic heating,” Nano Lett. 14(1), 6–12 (2014).NALEFD1530-6984 http://dx.doi.org/10.1021/nl403419e Google Scholar

21. H. Huanget al., “Remote control of ion channels and neurons through magnetic-field heating of nanoparticles,” Nat. Nanotechnol. 5(8), 602–606 (2010).1748-3387 http://dx.doi.org/10.1038/nnano.2010.125 Google Scholar

22. C. Hoffmannet al., “Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles,” Nat. Nanotechnol. 8(3), 199–205 (2013).1748-3387 http://dx.doi.org/10.1038/nnano.2012.246 Google Scholar

23. C. Hoffmannet al., “Magnetic control of protein spatial patterning to direct microtubule self-assembly,” ACS Nano 7(11), 9647–9654 (2013).1936-0851 http://dx.doi.org/10.1021/nn4022873 Google Scholar

24. L. Bonnemayet al., “Engineering spatial gradients of signaling proteins using magnetic nanoparticles,” Nano Lett. 13(11), 5147–5152 (2013).NALEFD1530-6984 http://dx.doi.org/10.1021/nl402356b Google Scholar

25. N. ErathodiyilJ. Y. Ying, “Functionalization of inorganic nanoparticles for bioimaging applications,” Acc. Chem. Res. 44(10), 925–935 (2011).ACHRE40001-4842 http://dx.doi.org/10.1021/ar2000327 Google Scholar

26. I. WillnerB. Willner, “Biomolecule-based nanomaterials and nanostructures,” Nano Lett. 10(10), 3805–3815 (2010).NALEFD1530-6984 http://dx.doi.org/10.1021/nl102083j Google Scholar

27. Z. Aliet al., “Multifunctional nanoparticles for dual imaging,” Anal. Chem. 83(8), 2877–2882 (2011).ANCHAM0003-2700 http://dx.doi.org/10.1021/ac103261y Google Scholar

28. V. Bagalkotet al., “Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer,” Nano Lett. 7(10), 3065–3070 (2007).NALEFD1530-6984 http://dx.doi.org/10.1021/nl071546n Google Scholar

29. H. S. Choet al., “Fluorescent, superparamagnetic nanospheres for drug storage, targeting, and imaging: a multifunctional nanocarrier system for cancer diagnosis and treatment,” ACS Nano 4(9), 5398–5404 (2010).1936-0851 http://dx.doi.org/10.1021/nn101000e Google Scholar

30. N.-H. Choet al., “A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy,” Nat. Nanotechnol. 6(10), 675–682 (2011).1748-3387 http://dx.doi.org/10.1038/nnano.2011.149 Google Scholar

31. Z. Fanet al., “Multifunctional plasmonic shell-magnetic core nanoparticles for targeted diagnostics, isolation, and photothermal destruction of tumor cells,” ACS Nano 6(2), 1065–1073 (2012).1936-0851 http://dx.doi.org/10.1021/nn2045246 Google Scholar

32. M. Dahanet al., “Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking,” Science 302(5644), 442–445 (2003).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.1088525 Google Scholar

33. R. Huet al., “Rational design of multimodal and multifunctional InP quantum dot nanoprobes for cancer: in vitro and in vivo applications,” RSC Adv. 3(22), 8495–8503 (2013).RSCACL2046-2069 http://dx.doi.org/10.1039/c3ra23169k Google Scholar

34. Y. Yanget al., “In-vitro and in-vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles,” Angew. Chem. Int. Ed. 51(13), 3125–3129 (2012).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.v51.13 Google Scholar

35. L. Shanget al., “Ultra-small fluorescent metal nanoclusters: synthesis and biological applications,” Nano Today 6(4), 401–418 (2011).1748-0132 http://dx.doi.org/10.1016/j.nantod.2011.06.004 Google Scholar

36. K. Kimet al., “Photoacoustic imaging of early inflammatory response using gold nanorods,” Appl. Phys. Lett. 90(22), 223901 (2007).APPLAB0003-6951 http://dx.doi.org/10.1063/1.2743752 Google Scholar

37. C. Baoet al., “Gold nanoprisms as optoacoustic signal nanoamplifiers for in vivo bioimaging of gastrointestinal cancers,” Small 9(1), 68–74 (2013).1613-6829 http://dx.doi.org/10.1002/smll.v9.1 Google Scholar

38. J. Y. Parket al., “Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images,” ACS Nano 3(11), 3663–3669 (2009).1936-0851 http://dx.doi.org/10.1021/nn900761s Google Scholar

39. B. Pelazet al., “Tailoring the synthesis and heating ability of gold nanoprisms for bioapplications,” Langmuir 28(24), 8965–8970 (2012).LANGD50743-7463 http://dx.doi.org/10.1021/la204712u Google Scholar

40. C. M. Hesselet al., “Copper selenide nanocrystals for photothermal therapy,” Nano Lett. 11(6), 2560–2566 (2011).NALEFD1530-6984 http://dx.doi.org/10.1021/nl201400z Google Scholar

41. K. Hayashiet al., “Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment,” Theranostics 3(6), 366–376 (2013).THERDS1838-7640 http://dx.doi.org/10.7150/thno.5860 Google Scholar

42. N. M. Idriset al., “In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers,” Nat. Med. 18(10), 1580–1585 (2012).1078-8956 http://dx.doi.org/10.1038/nm.2933 Google Scholar

43. S. I. Stoevaet al., “Multiplexed detection of protein cancer markers with biobarcoded nanoparticle probes,” J. Am. Chem. Soc. 128(26), 8378–8379 (2006).JACSAT0002-7863 http://dx.doi.org/10.1021/ja0613106 Google Scholar

44. C. L. Zavaletaet al., “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. 106(32), 13511–13516 (2009).PMASAX0096-9206 http://dx.doi.org/10.1073/pnas.0813327106 Google Scholar

45. E. Poloet al., “Plasmonic-driven thermal sensing: ultralow detection of cancer markers,” Chem. Commun. 49(35), 3676–3678 (2013).CHCOFS1364-548X http://dx.doi.org/10.1039/c3cc39112d Google Scholar

46. J. M. Perezet al., “Magnetic relaxation switches capable of sensing molecular interactions,” Nat. Biotechnol. 20(8), 816–820 (2002).NABIF91087-0156 http://dx.doi.org/10.1038/nbt720 Google Scholar

47. M. Riedelet al., “Photoelectrochemical sensor based on quantum dots and sarcosine oxidase,” Chem. Phys. Chem. 14(10), 2338–2342 (2013).CPCHFT1439-4235 http://dx.doi.org/10.1002/cphc.201201036 Google Scholar

48. G. A. Zelada-Guillénet al., “Immediate detection of living bacteria at ultralow concentrations using a carbon nanotube based potentiometric aptasensor,” Angew. Chem. Int. Ed. 48(40), 7334–7337 (2009).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.v48:40 Google Scholar

49. I. L. Medintzet al., “Quantum dot bioconjugates for imaging, labelling and sensing,” Nat. Mater. 4(6), 435–446 (2005).NMAACR1476-1122 http://dx.doi.org/10.1038/nmat1390 Google Scholar

50. S. Puertaset al., “Taking advantage of unspecific interactions to produce highly active magnetic nanoparticle-antibody conjugates,” ACS Nano 5(6), 4521–4528 (2011).1936-0851 http://dx.doi.org/10.1021/nn200019s Google Scholar

51. Z. Daiet al., “Nanoparticle-based sensing of glycan-lectin interactions,” J. Am. Chem. Soc. 128(31), 10018–10019 (2006).JACSAT0002-7863 http://dx.doi.org/10.1021/ja063565p Google Scholar

52. M. Reynoldset al., “Multivalent gold glycoclusters: high affinity molecular recognition by bacterial lectin PA-IL,” Chemistry 18(14), 4264–4273 (2012).CHRYAQ0009-305X http://dx.doi.org/10.1002/chem.v18.14 Google Scholar

53. M. Moroset al., “Monosaccharides versus PEG-functionalized NPs: influence in the cellular uptake,” ACS Nano 6(2), 1565–1577 (2012).1936-0851 http://dx.doi.org/10.1021/nn204543c Google Scholar

54. K. K. Nget al., “Lipoprotein-inspired nanoparticles for cancer theranostics,” Acc. Chem. Res. 44(10), 1105–1113 (2011).ACHRE40001-4842 http://dx.doi.org/10.1021/ar200017e Google Scholar

55. Q. Songet al., “Lipoprotein-based nanoparticles rescue the memory loss of mice with Alzheimer’s disease by accelerating the clearance of amyloid-beta,” ACS Nano 8(3), 2345–2359 (2014).1936-0851 http://dx.doi.org/10.1021/nn4058215 Google Scholar

56. E. C. Dreadenet al., “Tamoxifen-poly(ethylene glycol)-thiol gold nanoparticle conjugates: enhanced potency and selective delivery for breast cancer treatment,” Bioconjug. Chem. 20(12), 2247–2253 (2009).BCCHES1043-1802 http://dx.doi.org/10.1021/bc9002212 Google Scholar

57. M. Daset al., “Intranuclear drug delivery and effective in vivo cancer therapy via estradiol-PEG-appended multiwalled carbon nanotubes,” Mol. Pharm. 10(9), 3404–3416 (2013).1543-8384 http://dx.doi.org/10.1021/mp4002409 Google Scholar

58. C. Wanget al., “Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy,” Biomaterials 32(4), 1110–1120 (2011).BIMADU0142-9612 http://dx.doi.org/10.1016/j.biomaterials.2010.09.069 Google Scholar

59. F. Sonvicoet al., “Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments,” Bioconjug. Chem. 16(5), 1181–1188 (2005).BCCHES1043-1802 http://dx.doi.org/10.1021/bc050050z Google Scholar

60. C. R. Patraet al., “Fabrication and functional characterization of gold nanoconjugates for potential application in ovarian cancer,” J. Mater. Chem. 20(3), 547–554 (2010).JMACEP0959-9428 http://dx.doi.org/10.1039/b913224d Google Scholar

61. G. Zhanget al., “Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice,” Biomaterials 30(10), 1928–1936 (2009).BIMADU0142-9612 http://dx.doi.org/10.1016/j.biomaterials.2008.12.038 Google Scholar

62. T. Maldineyet al., “Effect of core diameter, surface coating, and PEG chain length on the biodistribution of persistent luminescence nanoparticles in mice,” ACS Nano 5(2), 854–862 (2011).1936-0851 http://dx.doi.org/10.1021/nn101937h Google Scholar

63. J. Linet al., “Photosensitizer-loaded gold vesicles with strong plasmonic coupling effect for imaging-guided photothermal/photodynamic therapy,” ACS Nano 7(6), 5320–5329 (2013).1936-0851 http://dx.doi.org/10.1021/nn4011686 Google Scholar

64. W. Yanget al., “Functionalizable and ultra stable nanoparticles coated with zwitterionic poly(carboxybetaine) in undiluted blood serum,” Biomaterials 30(29), 5617–5621 (2009).BIMADU0142-9612 http://dx.doi.org/10.1016/j.biomaterials.2009.06.036 Google Scholar

65. G. Jiaet al., “Novel zwitterionic-polymer-coated silica nanoparticles,” Langmuir 25(5), 3196–3199 (2009).LANGD50743-7463 http://dx.doi.org/10.1021/la803737c Google Scholar

66. P. del Pinoet al., “Gene silencing mediated by magnetic lipospheres tagged with small interfering RNA,” Nano Lett. 10(10), 3914–3921 (2010).NALEFD1530-6984 http://dx.doi.org/10.1021/nl102485v Google Scholar

67. M. Ochset al., “Light-addressable capsules as caged compound matrix for controlled in vitro release,” Angew. Chem. Int. Ed. 52(2), 695–699 (2013).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.201206696 Google Scholar

68. M. E. Daviset al., “Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles,” Nature 464(7291), 1067–1070 (2010).NATUAS0028-0836 http://dx.doi.org/10.1038/nature08956 Google Scholar

69. R. Elghanianet al., “Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles,” Science 277(5329), 1078–1081 (1997).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.277.5329.1078 Google Scholar

70. J. S. Leeet al., “Colorimetric detection of mercuric ion (Hg2+) in aqueous media using DNA-functionalized gold nanoparticles,” Angew. Chem. Int. Ed. 46(22), 4093–4096 (2007).ACIEAY0570-0833 http://dx.doi.org/10.1002/(ISSN)1521-3773 Google Scholar

71. J. M. Namet al., “Bio-bar-code-based DNA detection with PCR-like sensitivity,” J. Am. Chem. Soc. 126(19), 5932–5933 (2004).JACSAT0002-7863 http://dx.doi.org/10.1021/ja049384+ Google Scholar

72. J. J. Storhoffet al., “One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes,” J. Am. Chem. Soc. 120(9), 1959–1964 (1998).JACSAT0002-7863 http://dx.doi.org/10.1021/ja972332i Google Scholar

73. X. Y. Xuet al., “Colorimetric Cu2+ detection using DNA-modified gold-nanoparticle aggregates as probes and click chemistry,” Small 6(5), 623–626 (2010).1613-6829 http://dx.doi.org/10.1002/smll.v6:5 Google Scholar

74. C. Sansonet al., “Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy,” ACS Nano 5(2), 1122–1140 (2011).1936-0851 http://dx.doi.org/10.1021/nn102762f Google Scholar

75. H. Parket al., “Multifunctional nanoparticles for combined doxorubicin and photothermal treatments,” ACS Nano 3(10), 2919–2926 (2009).1936-0851 http://dx.doi.org/10.1021/nn900215k Google Scholar

76. C. M. Cobleyet al., “Gold nanostructures: a class of multifunctional materials for biomedical applications,” Chem. Soc. Rev. 40(1), 44–56 (2011).CSRVBR0306-0012 http://dx.doi.org/10.1039/b821763g Google Scholar

77. S. Cuiet al., “In vivo targeted deep-tissue photodynamic therapy based on near-infrared light triggered upconversion nanoconstruct,” ACS Nano 7(1), 676–688 (2013).1936-0851 http://dx.doi.org/10.1021/nn304872n Google Scholar

78. P. Zrazhevskiyet al., “Designing multifunctional quantum dots for bioimaging, detection, and drug delivery,” Chem. Soc. Rev. 39(11), 4326–4354 (2010).CSRVBR0306-0012 http://dx.doi.org/10.1039/b915139g Google Scholar

79. M. Colomboet al., “Biological applications of magnetic nanoparticles,” Chem. Soc. Rev. 41(11), 4306–4334 (2012).CSRVBR0306-0012 http://dx.doi.org/10.1039/c2cs15337h Google Scholar

80. J. Xieet al., “PET/NIRF/MRI triple functional iron oxide nanoparticles,” Biomaterials 31(11), 3016–3022 (2010).BIMADU0142-9612 http://dx.doi.org/10.1016/j.biomaterials.2010.01.010 Google Scholar

81. E. S. Choet al., “Ultrasensitive detection of toxic cations through changes in the tunnelling current across films of striped nanoparticles,” Nat. Mater. 11(11), 978–985 (2012).NMAACR1476-1122 http://dx.doi.org/10.1038/nmat3406 Google Scholar

82. Y. Yanget al., “NIR light controlled photorelease of siRNA and its targeted intracellular delivery based on upconversion nanoparticles,” Nanoscale 5(1), 231–238 (2013).1556-276X http://dx.doi.org/10.1039/c2nr32835f Google Scholar

83. M. K. G. Jayakumaret al., “Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers,” Proc. Natl. Acad. Sci. 109(22), 8483–8488 (2012).PMASAX0096-9206 http://dx.doi.org/10.1073/pnas.1114551109 Google Scholar

84. X.-F. Qiaoet al., “Triple-functional core-shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro,” Nanoscale 4(15), 4611–4623 (2012).1556-276X http://dx.doi.org/10.1039/c2nr30938f Google Scholar

85. Y. Jin, “Multifunctional compact hybrid Au nanoshells: a new generation of nanoplasmonic probes for biosensing, imaging, and controlled release,” Acc. Chem. Res. 47(1), 138–148 (2014).ACHRE40001-4842 http://dx.doi.org/10.1021/ar400086e Google Scholar

86. K. Yanget al., “Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles,” Adv. Mater. 24(14), 1868–1872 (2012).ADVMEW0935-9648 http://dx.doi.org/10.1002/adma.v24.14 Google Scholar

87. A. Al Zakiet al., “Gold-loaded polymeric micelles for computed tomography-guided radiation therapy treatment and radiosensitization,” ACS Nano 8(1), 104–112 (2014).1936-0851 http://dx.doi.org/10.1021/nn405701q Google Scholar

88. Z. Zhanget al., “Near-infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging,” Adv. Mater. 25(28), 3869–3880 (2013).ADVMEW0935-9648 http://dx.doi.org/10.1002/adma.v25.28 Google Scholar

89. D. Boyeret al., “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297(5584), 1160–1163 (2002).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.1073765 Google Scholar

90. G. Baffouet al., “Thermal imaging of nanostructures by quantitative optical phase analysis,” ACS Nano 6(3), 2452–2458 (2012).1936-0851 http://dx.doi.org/10.1021/nn2047586 Google Scholar

91. L. Rodriguez-Lorenzoet al., “Intracellular mapping with SERS-encoded gold nanostars,” Integr. Biol. 3(9), 922–926 (2011).1757-9708 http://dx.doi.org/10.1039/c1ib00029b Google Scholar

92. J. Mogeret al., “Imaging metal oxide nanoparticles in biological structures with CARS microscopy,” Opt. Express 16(5), 3408–3419 (2008).OPEXFF1094-4087 http://dx.doi.org/10.1364/OE.16.003408 Google Scholar

93. Y. Jianget al., “Bioimaging with two-photon-induced luminescence from triangular nanoplates and nanoparticle aggregates of gold,” Adv. Mater. 21(22), 2309–2313 (2009).ADVMEW0935-9648 http://dx.doi.org/10.1002/adma.v21:22 Google Scholar

94. L. E. Brus, “A simple model for the ionization potential, electron affinity, and aqueous redox potentials of small semiconductor crystallites,” J. Chem. Phys. 79(11), 5566–5571 (1983).JCPSA60021-9606 http://dx.doi.org/10.1063/1.445676 Google Scholar

95. C. B. Murrayet al., “Synthesis and characterization of nearly monodisperse CdE (E=sulfur, selenium, tellurium) semiconductor nanocrystallites,” J. Am. Chem. Soc. 115(19), 8706–8715 (1993).JACSAT0002-7863 http://dx.doi.org/10.1021/ja00072a025 Google Scholar

96. A. P. Alivisatos, “Semiconductor clusters, nanocrystals, and quantum dots,” Science 271(5251), 933–937 (1996).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.271.5251.933 Google Scholar

97. H. Welleret al., “Photochemistry of semiconductor colloids—properties of extremely small particles of Cd3P2 and Zn3P2,” Chem. Phys. Lett. 117(5), 485–488 (1985).CHPLBC0009-2614 http://dx.doi.org/10.1016/0009-2614(85)80287-6 Google Scholar

98. M. A. Reedet al., “Observation of discrete electronic states in a zero-dimensional semiconductor nanostructure,” Phys. Rev. Lett. 60(6), 535–537 (1988).PRLTAO0031-9007 http://dx.doi.org/10.1103/PhysRevLett.60.535 Google Scholar

99. A. I. Ekimovet al., “Quantum size effect in semiconductor microcrystals,” Solid State Commun. 56(11), 921–924 (1985).SSCOA40038-1098 http://dx.doi.org/10.1016/S0038-1098(85)80025-9 Google Scholar

100. P. M. AllenM. G. Bawendi, “Ternary I-III-VI quantum dots luminescent in the red to near-infrared,” J. Am. Chem. Soc. 130(29), 9240–9241 (2008).JACSAT0002-7863 http://dx.doi.org/10.1021/ja8036349 Google Scholar

101. P. M. Allenet al., “InAs(ZnCdS) quantum dots optimized for biological imaging in the near-infrared,” J. Am. Chem. Soc. 132(2), 470–471 (2010).JACSAT0002-7863 http://dx.doi.org/10.1021/ja908250r Google Scholar

102. T. Ponset al., “Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity,” ACS Nano 4(5), 2531–2538 (2010).1936-0851 http://dx.doi.org/10.1021/nn901421v Google Scholar

103. D. K. Harriset al., “Synthesis of cadmium arsenide quantum dots luminescent in the infrared,” J. Am. Chem. Soc. 133(13), 4676–4679 (2011).JACSAT0002-7863 http://dx.doi.org/10.1021/ja1101932 Google Scholar

104. E. Cassetteet al., “Design of new quantum dot materials for deep tissue infrared imaging,” Adv. Drug Delivery Rev. 65(5), 719–731 (2013).ADDREP0169-409X http://dx.doi.org/10.1016/j.addr.2012.08.016 Google Scholar

105. C. Kirchneret al., “Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles,” Nano Lett. 5(2), 331–338 (2005).NALEFD1530-6984 http://dx.doi.org/10.1021/nl047996m Google Scholar

106. W. Liuet al., “Compact biocompatible quantum dots via RAFT-mediated synthesis of imidazole-based random copolymer ligand,” J. Am. Chem. Soc. 132(2), 472–483 (2010).JACSAT0002-7863 http://dx.doi.org/10.1021/ja908137d Google Scholar

107. J. FanP. K. Chu, “Group IV nanoparticles: synthesis, properties, and biological applications,” Small 6(19), 2080–2098 (2010).1613-6829 http://dx.doi.org/10.1002/smll.201000543 Google Scholar

108. V. N. Mochalinet al., “The properties and applications of nanodiamonds,” Nat. Nanotechnol. 7(1), 11–23 (2012).1748-3387 http://dx.doi.org/10.1038/nnano.2011.209 Google Scholar

109. A. Magrezet al., “Cellular toxicity of carbon-based nanomaterials,” Nano Lett. 6(6), 1121–1125 (2006).NALEFD1530-6984 http://dx.doi.org/10.1021/nl060162e Google Scholar

110. F. Wanget al., “Upconversion nanoparticles in biological labeling, imaging, and therapy,” Analyst 135(8), 1839–1854 (2010).ANLYAG0365-4885 http://dx.doi.org/10.1039/c0an00144a Google Scholar

111. J.-C. BoyerF. C. J. M. van Veggel, “Absolute quantum yield measurements of colloidal NaYF4Er3+, Yb3+ upconverting nanoparticles,” Nanoscale 2(8), 1417–1419 (2010).1556-276X http://dx.doi.org/10.1039/c0nr00253d Google Scholar

112. S. H. Yauet al., “An ultrafast look at Au nanoclusters,” Acc. Chem. Res. 46(7), 1506–1516 (2013).ACHRE40001-4842 http://dx.doi.org/10.1021/ar300280w Google Scholar

113. C. Wanget al., “Near infrared Ag/Au alloy nanoclusters: tunable photoluminescence and cellular imaging,” J. Colloid Interface Sci. 416, 274–279 (2014).JCISA50021-9797 http://dx.doi.org/10.1016/j.jcis.2013.11.011 Google Scholar

114. H.-H. Wanget al., “Fluorescent gold nanoclusters as a biocompatible marker for in vitro and in vivo tracking of endothelial cells,” ACS Nano 5(6), 4337–4344 (2011).1936-0851 http://dx.doi.org/10.1021/nn102752a Google Scholar

115. V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7(8), 603–614 (2010).1548-7091 http://dx.doi.org/10.1038/nmeth.1483 Google Scholar

116. A. De La Zerdaet al., “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).1748-3387 http://dx.doi.org/10.1038/nnano.2008.231 Google Scholar

117. C. Kimet al., “In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages,” ACS Nano 4(8), 4559–4564 (2010).1936-0851 http://dx.doi.org/10.1021/nn100736c Google Scholar

118. K. A. Homanet al., “Silver nanoplate contrast agents for in vivo molecular photoacoustic imaging,” ACS Nano 6(1), 641–650 (2012).1936-0851 http://dx.doi.org/10.1021/nn204100n Google Scholar

119. A. Feiset al., “Photoacoustic excitation profiles of gold nanoparticles,” Photoacoustics 2(1), 47–53 (2014).2213-5979 http://dx.doi.org/10.1016/j.pacs.2013.12.001 Google Scholar

120. N. Lozanoet al., “Liposome-gold nanorod hybrids for high-resolution visualization deep in tissues,” J. Am. Chem. Soc. 134(32), 13256–13258 (2012).JACSAT0002-7863 http://dx.doi.org/10.1021/ja304499q Google Scholar

121. D. A. Nedosekinet al., “Ultra-fast photoacoustic flow cytometry with a 0.5 MHz pulse repetition rate nanosecond laser,” Opt. Express 18(8), 8605–8620 (2010).OPEXFF1094-4087 http://dx.doi.org/10.1364/OE.18.008605 Google Scholar

125. G. Honget al., “Multifunctional in vivo vascular imaging using near-infrared II fluorescence,” Nat. Med. 18(12), 1841–1846 (2012).1078-8956 http://dx.doi.org/10.1038/nm.2995 Google Scholar

122. B. Zhuet al., “Preparation of carbon nanodots from single chain polymeric nanoparticles and theoretical investigation of the photoluminescence mechanism,” J. Mater. Chem. C 1(3), 580–586 (2013).JMACEP0959-9428 http://dx.doi.org/10.1039/c2tc00140c Google Scholar

123. F. A. Inamet al., “Emission and nonradiative decay of nanodiamond NV centers in a low refractive index environment,” ACS Nano 7(5), 3833–3843 (2013).1936-0851 http://dx.doi.org/10.1021/nn304202g Google Scholar

124. D. Jurbergset al., “Silicon nanocrystals with ensemble quantum yields exceeding 60%,” Appl. Phys. Lett. 88(23), 233116 (2006).APPLAB0003-6951 http://dx.doi.org/10.1063/1.2210788 Google Scholar

126. M. HaaseH. Schäfer, “Upconverting nanoparticles,” Angew. Chem. Int. Ed. 50(26), 5808–5829 (2011).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.v50.26 Google Scholar

127. S. Wanget al., “A 200-fold quantum yield boost in the photoluminescence of silver-doped AgxAu25x nanoclusters: the 13th silver atom matters,” Angew. Chem. Int. Ed. 53(9), 2376–2380 (2014).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.201307480 Google Scholar

128. B. H. Kimet al., “Large-scale synthesis of uniform and extremely small-sized iron oxide nanoparticles for high-resolution T1 magnetic resonance imaging contrast agents,” J. Am. Chem. Soc. 133(32), 12624–12631 (2011).JACSAT0002-7863 http://dx.doi.org/10.1021/ja203340u Google Scholar

129. J. Xiaoet al., “Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging,” Sci. Rep. 3, 3424 (2013).SRCEC3 http://dx.doi.org/10.1038/srep03424 Google Scholar

130. R. Haoet al., “Synthesis, functionalization, and biomedical applications of multifunctional magnetic nanoparticles,” Adv. Mater. 22(25), 2729–2742 (2010).ADVMEW0935-9648 http://dx.doi.org/10.1002/adma.201000260 Google Scholar

131. P. R. GilW. J. Parak, “Composite nanoparticles take aim at cancer,” ACS Nano 2(11), 2200–2205 (2008).1936-0851 http://dx.doi.org/10.1021/nn800716j Google Scholar

132. F. Menget al., “Intracellular drug release nanosystems,” Mater. Today 15(10), 436–442 (2012).MATOBY0096-4867 http://dx.doi.org/10.1016/S1369-7021(12)70195-5 Google Scholar

133. A. BoltassevaH. A. Atwater, “Low-loss plasmonic metamaterials,” Science 331(6015), 290–291 (2011).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.1198258 Google Scholar

134. A. M. Alkilanyet al., “Gold nanorods: their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions,” Adv. Drug Deliv. Rev. 64(2), 190–199 (2012).ADDREP0169-409X http://dx.doi.org/10.1016/j.addr.2011.03.005 Google Scholar

135. A. M. Javieret al., “Photoactivated release of cargo from the cavity of polyelectrolyte capsules to the cytosol of cells,” Langmuir 24(21), 12517–12520 (2008).LANGD50743-7463 http://dx.doi.org/10.1021/la802448z Google Scholar

136. R. Huschkaet al., “Gene silencing by gold nanoshell-mediated delivery and laser-triggered release of antisense oligonucleotide and siRNA,” ACS Nano 6(9), 7681–7691 (2012).1936-0851 http://dx.doi.org/10.1021/nn301135w Google Scholar

137. N. J. Durret al., “Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods,” Nano Lett. 7(4), 941–945 (2007).NALEFD1530-6984 http://dx.doi.org/10.1021/nl062962v Google Scholar

138. O. Neumannet al., “Compact solar autoclave based on steam generation using broadband light-harvesting nanoparticles,” Proc. Natl. Acad. Sci. 110(29), 11677–11681 (2013).PMASAX0096-9206 http://dx.doi.org/10.1073/pnas.1310131110 Google Scholar

139. A. L. Antariset al., “Ultra-low doses of chirality sorted (6,5) carbon nanotubes for simultaneous tumor imaging and photothermal therapy,” ACS Nano 7(4), 3644–3652 (2013).1936-0851 http://dx.doi.org/10.1021/nn4006472 Google Scholar

140. D. Yooet al., “Theranostic magnetic nanoparticles,” Acc. Chem. Res. 44(10), 863–874 (2011).ACHRE40001-4842 http://dx.doi.org/10.1021/ar200085c Google Scholar

141. R. Di Coratoet al., “Magnetic nanobeads decorated with silver nanoparticles as cytotoxic agents and photothermal probes,” Small 8(17), 2731–2742 (2012).1613-6829 http://dx.doi.org/10.1002/smll.v8.17 Google Scholar

142. Y. Liet al., “Copper sulfide nanoparticles for photothermal ablation of tumor cells,” Nanomedicine 5(8), 1161–1171 (2010).1743-5889 http://dx.doi.org/10.2217/nnm.10.85 Google Scholar

143. W. Liet al., “CuTe nanocrystals: shape and size control, plasmonic properties, and use as SERS probes and photothermal agents,” J. Am. Chem. Soc. 135(19), 7098–7101 (2013).JACSAT0002-7863 http://dx.doi.org/10.1021/ja401428e Google Scholar

144. K. Yanget al., “Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy,” Nano Lett. 10(9), 3318–3323 (2010).NALEFD1530-6984 http://dx.doi.org/10.1021/nl100996u Google Scholar

145. S. Lalet al., “Nanoshell-enabled photothermal cancer therapy: impending clinical impact,” Acc. Chem. Res. 41(12), 1842–1851 (2008).ACHRE40001-4842 http://dx.doi.org/10.1021/ar800150g Google Scholar

146. S. N. Bhatiaet al., “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res. 69(9), 3892–3900 (2009).CNREA80008-5472 http://dx.doi.org/10.1158/0008-5472.CAN-08-4242 Google Scholar

147. D. P. O’Nealet al., “Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles,” Cancer Lett. 209(2), 171–176 (2004).CALEDQ0304-3835 http://dx.doi.org/10.1016/j.canlet.2004.02.004 Google Scholar

148. R. Huschkaet al., “Light-induced release of DNA from gold nanoparticles: nanoshells and nanorods,” J. Am. Chem. Soc. 133(31), 12247–12255 (2011).JACSAT0002-7863 http://dx.doi.org/10.1021/ja204578e Google Scholar

149. R. Huschkaet al., “Visualizing light-triggered release of molecules inside living cells,” Nano Lett. 10(10), 4117–4122 (2010).NALEFD1530-6984 http://dx.doi.org/10.1021/nl102293b Google Scholar

150. A. Barhoumiet al., “Light-induced release of DNA from plasmon-resonant nanoparticles: towards light-controlled gene therapy,” Chem. Phys. Lett. 482(4–6), 171–179 (2009).CHPLBC0009-2614 http://dx.doi.org/10.1016/j.cplett.2009.09.076 Google Scholar

151. A. G. Skirtachet al., “Laser-induced release of encapsulated materials inside living cells,” Angew. Chem. Int. Ed. 45(28), 4612–4617 (2006).ACIEAY0570-0833 http://dx.doi.org/10.1002/(ISSN)1521-3773 Google Scholar

152. S. J. LeungM. Romanowski, “Molecular catch and release: controlled delivery using optical trapping with light-responsive liposomes,” Adv. Mater. 24(47), 6380–6383 (2012).ADVMEW0935-9648 http://dx.doi.org/10.1002/adma.201202180 Google Scholar

153. A. M. Javieret al., “Photoactivated release of cargo from the cavity of polyelectrolyte capsules to the cytosol of cells,” Langmuir 24(21), 12517–12520 (2008).LANGD50743-7463 http://dx.doi.org/10.1021/la802448z Google Scholar

154. S. Carregal-Romeroet al., “NIR-light triggered delivery of macromolecules into the cytosol,” J. Control. Release 159(1), 120–127 (2012).JCREEC0168-3659 http://dx.doi.org/10.1016/j.jconrel.2011.12.013 Google Scholar

155. A.-H. Luet al., “Magnetic nanoparticles: synthesis, protection, functionalization, and application,” Angew. Chem. Int. Ed. 46(8), 1222–1244 (2007).ACIEAY0570-0833 http://dx.doi.org/10.1002/(ISSN)1521-3773 Google Scholar

156. M. Johannsenet al., “Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique,” Int. J. Hyperthermia 21(7), 637–647 (2005).IJHYEQ0265-6736 http://dx.doi.org/10.1080/02656730500158360 Google Scholar

157. M. Johannsenet al., “Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution,” Eur. Urol. 52(6), 1653 (2007).EUURAV0302-2838 http://dx.doi.org/10.1016/j.eururo.2006.11.023 Google Scholar

158. A. Jordanet al., “Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia,” J. Magn. Magn. Mater. 225(1–2), 118–126 (2001).JMMMDC0304-8853 http://dx.doi.org/10.1016/S0304-8853(00)01239-7 Google Scholar

159. A. Jordanet al., “Magnetic fluid hyperthermia (MFH): cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles,” J. Magn. Magn. Mater. 201(1–3), 413–419 (1999).JMMMDC0304-8853 http://dx.doi.org/10.1016/S0304-8853(99)00088-8 Google Scholar

160. A. Jordanet al., “Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia,” Int. J. Hyperthermia 9(1), 51–68 (1993).IJHYEQ0265-6736 http://dx.doi.org/10.3109/02656739309061478 Google Scholar

161. B. Mehdaouiet al., “Optimal size of nanoparticles for magnetic hyperthermia: a combined theoretical and experimental study,” Adv. Funct. Mater. 21(23), 4573–4581 (2011).AFMDC61616-3028 http://dx.doi.org/10.1002/adfm.v21.23 Google Scholar

162. P. Guardiaet al., “Water-soluble iron oxide nanocubes with high values of specific absorption rate for cancer cell hyperthermia treatment,” ACS Nano 6(4), 3080–3091 (2012).1936-0851 http://dx.doi.org/10.1021/nn2048137 Google Scholar

163. K. H. Baeet al., “Chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes for magnetically modulated cancer hyperthermia,” ACS Nano 6(6), 5266–5273 (2012).1936-0851 http://dx.doi.org/10.1021/nn301046w Google Scholar

164. L.-M. Lacroixet al., “Stable single-crystalline body centered cubic Fe nanoparticles,” Nano Lett. 11(4), 1641–1645 (2011).NALEFD1530-6984 http://dx.doi.org/10.1021/nl200110t Google Scholar

165. A. Meffreet al., “A simple chemical route toward monodisperse iron carbide nanoparticles displaying tunable magnetic and unprecedented hyperthermia properties,” Nano Lett. 12(9), 4722–4728 (2012).NALEFD1530-6984 http://dx.doi.org/10.1021/nl302160d Google Scholar

166. E. Alphanderyet al., “Chains of magnetosomes extracted from AMB-1 magnetotactic bacteria for application in alternative magnetic field cancer therapy,” ACS Nano 5(8), 6279–6296 (2011).1936-0851 http://dx.doi.org/10.1021/nn201290k Google Scholar

167. R. Hergtet al., “Maghemite nanoparticles with very high AC-losses for application in RF-magnetic hyperthermia,” J. Magn. Magn. Mater. 270(3), 345–357 (2004).JMMMDC0304-8853 http://dx.doi.org/10.1016/j.jmmm.2003.09.001 Google Scholar

168. K. Maier-Hauffet al., “Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme,” J. Neurooncol. 103(2), 317–324 (2011).JNODD20167-594X http://dx.doi.org/10.1007/s11060-010-0389-0 Google Scholar

169. B. ThiesenA. Jordan, “Clinical applications of magnetic nanoparticles for hyperthermia,” Int. J. Hyperthermia 24(6), 467–474 (2008).IJHYEQ0265-6736 http://dx.doi.org/10.1080/02656730802104757 Google Scholar

170. M.-H. Kimet al., “Magnetic nanoparticle targeted hyperthermia of cutaneous staphylococcus aureus infection,” Ann. Biomed. Eng. 41(3), 598–609 (2013).ABMECF0090-6964 http://dx.doi.org/10.1007/s10439-012-0698-x Google Scholar

171. R. S. Rachakatlaet al., “Attenuation of mouse melanoma by A/C magnetic field after delivery of bi-magnetic nanoparticles by neural progenitor cells,” ACS Nano 4(12), 7093–7104 (2010).1936-0851 http://dx.doi.org/10.1021/nn100870z Google Scholar

172. A. Fernandez-Fernandezet al., “Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms,” Appl. Biochem. Biotechnol. 165(7–8), 1628–1651 (2011).ABIBDL0273-2289 http://dx.doi.org/10.1007/s12010-011-9383-z Google Scholar

173. K. Hayashiet al., “High-frequency, magnetic-field-responsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect,” ACS Appl. Mater. Interfaces 2(7), 1903–1911 (2010).AAMICK1944-8244 http://dx.doi.org/10.1021/am100237p Google Scholar

174. S. A. Stanleyet al., “Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice,” Science 336(6081), 604–608 (2012).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.1216753 Google Scholar

175. Y.-J. Kimet al., “A smart hyperthermia nanofiber with switchable drug release for inducing cancer apoptosis,” Adv. Funct. Mater. 23(46), 5753–5761 (2013).AFMDC61616-3028 http://dx.doi.org/10.1002/adfm.v23.46 Google Scholar

176. D. E. J. G. J. Dolmanset al., “Photodynamic therapy for cancer,” Nat. Rev. Cancer 3(5), 380–387 (2003).NRCAC41474-175X http://dx.doi.org/10.1038/nrc1071 Google Scholar

177. A. G. Arguinzonizet al., “Light harvesting and photoemission by nanoparticles for photodynamic therapy,” Part. Part. Syst. Charact. 31(1), 46–75 (2014).PPCHEZ0934-0866 http://dx.doi.org/10.1002/ppsc.v31.1 Google Scholar

178. J. F. Lovellet al., “Activatable photosensitizers for imaging and therapy,” Chem. Rev. 110(5), 2839–2857 (2010).CHREAY0009-2665 http://dx.doi.org/10.1021/cr900236h Google Scholar

179. P. Huanget al., “Photosensitizer-conjugated magnetic nanoparticles for in vivo simultaneous magnetofluorescent imaging and targeting therapy,” Biomaterials 32(13), 3447–3458 (2011).BIMADU0142-9612 http://dx.doi.org/10.1016/j.biomaterials.2011.01.032 Google Scholar

180. Y. Chenget al., “Deep penetration of a PDT drug into tumors by noncovalent drug-gold nanoparticle conjugates,” J. Am. Chem. Soc. 133(8), 2583–2591 (2011).JACSAT0002-7863 http://dx.doi.org/10.1021/ja108846h Google Scholar

181. S. b. Febvayet al., “Targeted cytosolic delivery of cell-impermeable compounds by nanoparticle-mediated, light-triggered endosome disruption,” Nano Lett. 10(6), 2211–2219 (2010).NALEFD1530-6984 http://dx.doi.org/10.1021/nl101157z Google Scholar

182. T. Stuchinskayaet al., “Targeted photodynamic therapy of breast cancer cells using antibody-phthalocyanine-gold nanoparticle conjugates,” Photochem. Photobiol. Sci. 10(5), 822–831 (2011).PPSHCB1474-905X http://dx.doi.org/10.1039/c1pp05014a Google Scholar

183. D. Bechetet al., “Nanoparticles as vehicles for delivery of photodynamic therapy agents,” Trends Biotechnol. 26(11), 612–621 (2008).TRBIDM0167-7799 http://dx.doi.org/10.1016/j.tibtech.2008.07.007 Google Scholar

184. N. A. Monteiro-Riviereet al., “Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study,” Toxicol. Sci. 123(1), 264–280 (2011).TOSCF21096-6080 http://dx.doi.org/10.1093/toxsci/kfr148 Google Scholar

185. N. Luet al., “Nano titanium dioxide photocatalytic protein tyrosine nitration: a potential hazard of TiO2 on skin,” Biochem. Biophys. Res. Commun. 370(4), 675–680 (2008).BBRCA90006-291X http://dx.doi.org/10.1016/j.bbrc.2008.04.010 Google Scholar

186. R. Caiet al., “Induction of cytotoxicity by photoexcited TiO2 particles,” Cancer Res. 52(8), 2346–2348 (1992).CNREA80008-5472 Google Scholar

187. T. L. ThompsonJ. T. Yates, “Surface science studies of the photoactivation of TiO2 new photochemical processes,” Chem. Rev. 106(10), 4428–4453 (2006).CHREAY0009-2665 http://dx.doi.org/10.1021/cr050172k Google Scholar

188. S. Georgeet al., “Role of Fe doping in tuning the band gap of TiO2 for the photo-oxidation-induced cytotoxicity paradigm,” J. Am. Chem. Soc. 133(29), 11270–11278 (2011).JACSAT0002-7863 http://dx.doi.org/10.1021/ja202836s Google Scholar

189. S. Yamaguchiet al., “Novel photodynamic therapy using water-dispersed TiO2-polyethylene glycol compound: evaluation of antitumor effect on glioma cells and spheroids in vitro,” Photochem. Photobiol. 86(4), 964–971 (2010).PHCBAP0031-8655 http://dx.doi.org/10.1111/j.1751-1097.2010.00742.x Google Scholar

190. L. Zenget al., “Multifunctional Fe3O4-TiO2 nanocomposites for magnetic resonance imaging and potential photodynamic therapy,” Nanoscale 5(5), 2107–2113 (2013).1556-276X http://dx.doi.org/10.1039/c3nr33978e Google Scholar

191. E. A. Rozhkovaet al., “A high-performance nanobio photocatalyst for targeted brain cancer therapy,” Nano Lett. 9(9), 3337–3342 (2009).NALEFD1530-6984 http://dx.doi.org/10.1021/nl901610f Google Scholar

192. A. C. S. Samiaet al., “Semiconductor quantum dots for photodynamic therapy,” J. Am. Chem. Soc. 125(51), 15736–15737 (2003).JACSAT0002-7863 http://dx.doi.org/10.1021/ja0386905 Google Scholar

193. A. Anaset al., “Photosensitized breakage and damage of DNA by CdSe-ZnS quantum dots,” J. Phys. Chem. B 112(32), 10005–10011 (2008).JPCBFK1520-6106 http://dx.doi.org/10.1021/jp8018606 Google Scholar

194. S. Dayalet al., “Observation of non-Förster-type energy-transfer behavior in quantum dot-phthalocyanine conjugates,” J. Am. Chem. Soc. 128(43), 13974–13975 (2006).JACSAT0002-7863 http://dx.doi.org/10.1021/ja063415e Google Scholar

195. J. M. Tsayet al., “Singlet oxygen production by peptide-coated quantum dot-photosensitizer conjugates,” J. Am. Chem. Soc. 129(21), 6865–6871 (2007).JACSAT0002-7863 http://dx.doi.org/10.1021/ja070713i Google Scholar

196. M. Idowuet al., “Photoinduced energy transfer between water-soluble CdTe quantum dots and aluminium tetrasulfonated phthalocyanine,” New J. Chem. 32(2), 290–296 (2008).NJCHE51144-0546 http://dx.doi.org/10.1039/b707808k Google Scholar

197. E. Yaghiniet al., “Fluorescence lifetime imaging and FRET-induced intracellular redistribution of Tat-conjugated quantum dot nanoparticles through interaction with a phthalocyanine photosensitiser,” Small 10(4), 782–792 (2014).1613-6829 http://dx.doi.org/10.1002/smll.201301459 Google Scholar

198. Z.-D. Qiet al., “Biocompatible CdSe quantum dot-based photosensitizer under two-photon excitation for photodynamic therapy,” J. Mater. Chem. 21(8), 2455–2458 (2011).JMACEP0959-9428 http://dx.doi.org/10.1039/c0jm03229h Google Scholar

199. C. Wanget al., “Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles,” Biomaterials 32(26), 6145–6154 (2011).BIMADU0142-9612 http://dx.doi.org/10.1016/j.biomaterials.2011.05.007 Google Scholar

200. D. K. ChatterjeeZ. Yong, “Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells,” Nanomedicine 3(1), 73–82 (2008).1743-5889 http://dx.doi.org/10.2217/17435889.3.1.73 Google Scholar

201. H. Guoet al., “Singlet oxygen-induced apoptosis of cancer cells using upconversion fluorescent nanoparticles as a carrier of photosensitizer,” Nanomed.: Nanotechnol., Biol. Med. 6(3), 486–495 (2010).1549-9634 http://dx.doi.org/10.1016/j.nano.2009.11.004 Google Scholar

202. J. Shanet al., “Pegylated composite nanoparticles containing upconverting phosphors and meso-tetraphenyl porphine (TPP) for photodynamic therapy,” Adv. Funct. Mater. 21(13), 2488–2495 (2011).AFMDC61616-3028 http://dx.doi.org/10.1002/adfm.201002516 Google Scholar

203. D. Peeret al., “Nanocarriers as an emerging platform for cancer therapy,” Nat. Nanotechnol. 2(12), 751–760 (2007).1748-3387 http://dx.doi.org/10.1038/nnano.2007.387 Google Scholar

204. J. P. Celliet al., “Imaging and photodynamic therapy: mechanisms, monitoring, and optimization,” Chem. Rev. 110(5), 2795–2838 (2010).CHREAY0009-2665 http://dx.doi.org/10.1021/cr900300p Google Scholar

205. C.-D. Chenet al., “Sensing capability of the localized surface plasmon resonance of gold nanorods,” Biosens. Bioelectron. 22(6), 926–932 (2007).BBIOE40956-5663 http://dx.doi.org/10.1016/j.bios.2006.03.021 Google Scholar

206. J. J. Storhoffet al., “Homogeneous detection of unamplified genomic DNA sequences based on colorimetric scatter of gold nanoparticle probes,” Nat. Biotechnol. 22(7), 883–887 (2004).NABIF91087-0156 http://dx.doi.org/10.1038/nbt977 Google Scholar

207. K. Fujiwaraet al., “Measurement of antibody binding to protein immobilized on gold nanoparticles by localized surface plasmon spectroscopy,” Anal. Bioanal. Chem. 386(3), 639–644 (2006).ABCNBP1618-2642 http://dx.doi.org/10.1007/s00216-006-0559-2 Google Scholar

208. F. Frederixet al., “Biosensing based on light absorption of nanoscaled gold and silver particles,” Anal. Chem. 75(24), 6894–6900 (2003).ANCHAM0003-2700 http://dx.doi.org/10.1021/ac0346609 Google Scholar

209. M. Kreuzeret al., “Colloidal-based localized surface plasmon resonance (LSPR) biosensor for the quantitative determination of stanozolol,” Anal. Bioanal. Chem. 391(5), 1813–1820 (2008).ABCNBP1618-2642 http://dx.doi.org/10.1007/s00216-008-2022-z Google Scholar

210. C. R. Yonzonet al., “A comparative analysis of localized and propagating surface plasmon resonance sensors: the binding of concanavalin A to a monosaccharide functionalized self-assembled monolayer,” J. Am. Chem. Soc. 126(39), 12669–12676 (2004).JACSAT0002-7863 http://dx.doi.org/10.1021/ja047118q Google Scholar

211. M. S. Cordrayet al., “Gold nanoparticle aggregation for quantification of oligonucleotides: optimization and increased dynamic range,” Anal. Biochem. 431(2), 99–105 (2012).ANBCA20003-2697 http://dx.doi.org/10.1016/j.ab.2012.09.013 Google Scholar

212. M. C. Estevezet al., “Trends and challenges of refractometric nanoplasmonic biosensors: a review,” Anal. Chim. Acta 806, 55–73 (2014).ACACAM0003-2670 http://dx.doi.org/10.1016/j.aca.2013.10.048 Google Scholar

213. B. Sepulvedaet al., “LSPR-based nanobiosensors,” Nano Today 4(3), 244–251 (2009).1748-0132 http://dx.doi.org/10.1016/j.nantod.2009.04.001 Google Scholar

214. W. L. Danielet al., “Colorimetric nitrite and nitrate detection with gold nanoparticle probes and kinetic end points,” J. Am. Chem. Soc. 131(18), 6362–6363 (2009).JACSAT0002-7863 http://dx.doi.org/10.1021/ja901609k Google Scholar

215. C. A. Mirkinet al., “A DNA-based method for rationally assembling nanoparticles into macroscopic materials,” Nature 382(6592), 607–609 (1996).NATUAS1096-0929 http://dx.doi.org/10.1038/382607a0 Google Scholar

216. S. Biet al., “Colorimetric logic gates based on supramolecular DNAzyme structures,” Angew. Chem. Int. Ed. 49(26), 4438–4442 (2010).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.201000840 Google Scholar

217. D. Liuet al., “Resettable, multi-readout logic gates based on controllably reversible aggregation of gold nanoparticles,” Angew. Chem. Int. Ed. 50(18), 4103–4107 (2011).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.v50.18 Google Scholar

218. W. Lihuaet al., “Biomolecular sensing via coupling DNA-based recognition with gold nanoparticles,” J. Phys. D: Appl. Phys. 42(20), 203001 (2009).JPAPBE0022-3727 http://dx.doi.org/10.1088/0022-3727/42/20/203001 Google Scholar

219. W. Zhaoet al., “DNA aptamer folding on gold nanoparticles:  from colloid chemistry to biosensors,” J. Am. Chem. Soc. 130(11), 3610–3618 (2008).JACSAT0002-7863 http://dx.doi.org/10.1021/ja710241b Google Scholar

220. H. Liet al., “Silver nanoparticle-enhanced fluorescence resonance energy transfer sensor for human platelet-derived growth factor-BB detection,” Anal. Chem. 85(9), 4492–4499 (2013).ANCHAM0003-2700 http://dx.doi.org/10.1021/ac400047d Google Scholar

221. E. Dulkeithet al., “Gold nanoparticles quench fluorescence by phase induced radiative rate suppression,” Nano Lett. 5(4), 585–589 (2005).NALEFD1530-6984 http://dx.doi.org/10.1021/nl0480969 Google Scholar

222. G. P. Acunaet al., “Fluorescence enhancement at docking sites of DNA-directed self-assembled nanoantennas,” Science 338(6106), 506–510 (2012).SCIEAS0036-8075 http://dx.doi.org/10.1126/science.1228638 Google Scholar

223. Y. Xinget al., “Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry,” Nat. Protoc. 2(5), 1152–1165 (2007).NPARDW1754-2189 http://dx.doi.org/10.1038/nprot.2007.107 Google Scholar

224. S. Carregal-Romeroet al., “Multiplexed sensing and imaging with colloidal nano- and microparticles,” Annu. Rev. Anal. Chem. 6(1), 53–81 (2013).ARACFU1936-1327 http://dx.doi.org/10.1146/annurev-anchem-062012-092621 Google Scholar

225. L. L. del Mercatoet al., “Multiplexed sensing of ions with barcoded polyelectrolyte capsules,” ACS Nano 5(12), 9668–9674 (2011).1936-0851 http://dx.doi.org/10.1021/nn203344w Google Scholar

226. A. Coto-Garcíaet al., “Nanoparticles as fluorescent labels for optical imaging and sensing in genomics and proteomics,” Anal. Bioanal. Chem. 399(1), 29–42 (2011).ABCNBP1618-2642 http://dx.doi.org/10.1007/s00216-010-4330-3 Google Scholar

227. L. Rodriguez-Lorenzoet al., “Multiplex optical sensing with surface-enhanced Raman scattering: a critical review,” Anal. Chim. Acta 745, 10–23 (2012).ACACAM0003-2670 http://dx.doi.org/10.1016/j.aca.2012.08.003 Google Scholar

228. R. Alvarez-Pueblaet al., “Light concentration at the nanometer scale,” J. Phys. Chem. Lett. 1(16), 2428–2434 (2010).1948-7185 http://dx.doi.org/10.1021/jz100820m Google Scholar

229. R. A. Alvarez-PueblaL. M. Liz-Marzan, “Traps and cages for universal SERS detection,” Chem. Soc. Rev. 41(1), 43–51 (2012).CSRVBR0306-0012 http://dx.doi.org/10.1039/c1cs15155j Google Scholar

230. R. A. Alvarez-PueblaL. M. Liz-Marzán, “SERS detection of small inorganic molecules and ions,” Angew. Chem. Int. Ed. 51(45), 11214–11223 (2012).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.201204438 Google Scholar

231. E. C. Le Ruet al., “A scheme for detecting every single target molecule with surface-enhanced Raman spectroscopy,” Nano Lett. 11(11), 5013–5019 (2011).NALEFD1530-6984 http://dx.doi.org/10.1021/nl2030344 Google Scholar

232. J. V. Jokerstet al., “Affibody-functionalized gold–silica nanoparticles for Raman molecular imaging of the epidermal growth factor receptor,” Small 7(5), 625–633 (2011).1613-6829 http://dx.doi.org/10.1002/smll.v7.5 Google Scholar

233. S. Barbosaet al., “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir 26(18), 14943–14950 (2010).LANGD50743-7463 http://dx.doi.org/10.1021/la102559e Google Scholar

234. L. Xuet al., “Regiospecific plasmonic assemblies for in situ Raman spectroscopy in live cells,” J. Am. Chem. Soc. 134(3), 1699–1709 (2012).JACSAT0002-7863 http://dx.doi.org/10.1021/ja2088713 Google Scholar

235. S. Gómez-Grañaet al., “Self-assembly of Au@Ag nanorods mediated by gemini surfactants for highly efficient SERS-active supercrystals,” Adv. Opt. Mater. 1(7), 477–481 (2013). http://dx.doi.org/10.1002/adom.201300162 Google Scholar

236. Z. Qinet al., “Significantly improved analytical sensitivity of lateral flow immunoassays by using thermal contrast,” Angew. Chem. Int. Ed. 51(18), 4358–4361 (2012).ACIEAY0570-0833 http://dx.doi.org/10.1002/anie.201200997 Google Scholar

237. G. A. Crespoet al., “Ion-selective electrodes using carbon nanotubes as ion-to-electron transducers,” Anal. Chem. 80(4), 1316–1322 (2008).ANCHAM0003-2700 http://dx.doi.org/10.1021/ac071156l Google Scholar

238. E. Katzet al., “Electroanalytical and bioelectroanalytical systems based on metal and semiconductor nanoparticles,” Electroanalysis 16(1–2), 19–44 (2004).ELANEU1040-0397 http://dx.doi.org/10.1002/(ISSN)1521-4109 Google Scholar

239. W. Khalidet al., “Immobilization of quantum dots via conjugated self-assembled monolayers and their application as a light-controlled sensor for the detection of hydrogen peroxide,” ACS Nano 5(12), 9870–9876 (2011).1936-0851 http://dx.doi.org/10.1021/nn2035582 Google Scholar

240. Z. Yueet al., “Quantum-dot-based photoelectrochemical sensors for chemical and biological detection,” ACS Appl. Mater. Interfaces 5(8), 2800–2814 (2013).AAMICK1944-8244 http://dx.doi.org/10.1021/am3028662 Google Scholar

Biography

Pablo del Pino graduated in physics from Universidad de Sevilla in 2002 and obtained his PhD degree at Technische Universität München, Germany, in 2007. He then joined the group of Wolfgang Parak as a postdoctoral fellow at the Ludwig-Maximilians-Universität München, Munich, Germany. From 2009 to 2013, he was a scientist (first postdoctoral researcher and in 2013, an independent ARAID junior researcher) at Institute of Nanoscience of Universidad de Zaragoza (INA, Zaragoza, Spain). In November 2013, he joined CIC biomaGUNE as senior postdoc in the Biofunctional Nanomaterials unit.

© The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Pablo del Pino, "Tailoring the interplay between electromagnetic fields and nanomaterials toward applications in life sciences: a review," Journal of Biomedical Optics 19(10), 101507 (10 July 2014). https://doi.org/10.1117/1.JBO.19.10.101507 . Submission:
JOURNAL ARTICLE
17 PAGES


SHARE
Back to Top