Nanoparticles doped with rare earth ions for biomedical imaging and infrared photodynamic therapy (IRPDT) have been
synthesized, characterized, and compared. Specifically, these nanoparticles utilize two primary modalities: near infrared
excitation and emission for imaging, and near infrared upconversion for photodynamic therapy. These nanoparticles are
optimized for both their infrared emission and upconversion energy transfer to a photoactive agent conjugated to the
surface. Finally, these nanoparticles are tested for toxicity, imaged in cells using the near infrared emission pathway, and
used for selective killing of cells through the upconversion driven IRPDT.
In this paper, we discuss the concept of an efficient infrared upconverting phosphor as an energy converting material that
could potentially improve the efficiency of Si solar cells in bifacial configuration. Basic spectroscopic studies of Yb and
Er-doped La<sub>2</sub>O<sub>2</sub>S phosphor was reported with particular attention to its upconversion properties under 1550 nm
excitation. Different concentrations of phosphors were synthesized by solid state flux fusion method. The phosphor
powders were well crystallized in a hexagonal shape with an average size 300-400 nm. The most efficient upconverting
sample (1%Yb: 9% Er doped La<sub>2</sub>O<sub>2</sub>S) was also studied under the illumination with infrared (IR) broad band spectrum
above 1000 nm. Our measurements show that even with an excitation power density of 0.159 W/cm2 using a tungsten
halogen lamp the material shows efficient upconversion corroborating the fact that the present phosphors could be
potential candidates for improving the efficiency of the present Si solar cells.
Yb and Er-doped Y<sub>2</sub>O<sub>2</sub>S phosphor was synthesized by solid state flux fusion method and their upconversion spectral
properties were studied as a function of different Yb concentrations. The solid state flux fusion results in well
crystallized hexagonal shaped phosphor particles of average size 3.8 μm. The detailed optical characterizations such as
absorption, emission, and fluorescence decay were performed to explore the emission processes in the UV-VIS-NIR as
well as to quantitatively estimate the fluorescence quantum yield. Upconversion spectral studies show that for all the
compositions, green emissions are stronger, particularly; the green emission intensity is 1.7 times stronger than the red
one with composition of 8 mol% Yb and 1 mol% Er. Mechanisms of upconversion by two photon and energy transfer
processes are interpreted and explained. The color coordinates are measured and the color tunability was analyzed as a
function of the 980 nm excitation power. Results show that the Y<sub>2</sub>O<sub>2</sub>S:Yb,Er phosphor offers power dependent color
tuning properties where the emission color can be tuned from 490 to 550 nm by simply changing the 980 nm excitation
power from 10 to 50 mW.
Highly efficient upconverting phosphors (NaYF4) doped with erbium ions are bio-conjugated and used for cancer
imaging and photodynamic therapy. Once they are conjugated, the particles are injected into mice to demonstrate that
cancer imaging with a near-infrared excitation source is possible. Finally, the particles are also conjugated with a
photosensitive molecule with strong absorption near the upconversion emission peak (~ 550nm). The upconversion
energy causes the photosensitive molecule to create highly reactive oxidative species, which puncture and kill the cell to
which it is attached. These particles are then used in a mouse model, and the size of the tumors is modeled as a function
of the dosage and duration of the photodynamic therapy.
Photodynamic agents such as Photofrin II (Photo II) utilized in photodynamic therapy
(PDT) possess a remarkable property to become preferentially retained within the
tumor's micro-environment. Upon the photo-agent's activation through visible light
photon absorption, the agents exert their cellular cytotoxicity through type II and type I
mechanistic pathways through extensive generation of reactive oxygen species (ROS):
singlet oxygen <sup>1</sup>O<sub>2</sub>, superoxide anion O<sub>2</sub>
-, and hydrogen peroxide H<sub>2</sub>O<sub>2</sub>, within the intratumoral
environment. Unfortunately, due to shallow visible light penetration depth
(~2mm to 5mm) in tissues, the PDT strategy currently has largely been restricted to the
treatments of surface tumors, such as the melanomas. Additional invasive strategies
through optical fibers are currently utilized in getting the visible light into the intended
deep seated targets within the body for PDT. In this communication, we report on a
novel strategy in utilizing "soft" energy diagnostic X-rays to indirectly activate Photo II
through X-ray induced luminescence from Gadolinium oxysulfide (20 micron dimension)
particles doped with Terbium: Gd<sub>2</sub>O<sub>2</sub>S:Tb. X-ray induced visible luminescence from
Gd<sub>2</sub>O<sub>2</sub>S:Tb particles was spectroscopically characterized and the ROS production levels
from clinically relevant concentration (10 μg/ml) of Photo II was quantified through
changes in the Vitamin C absorbance. ROS kinetics through X-ray induced luminescence
was found to be similar to the ROS kinetics from red He-Ne laser exposures used in the
clinics. Taken together, in-vitro findings herein provide the basis for future studies in
determining the safety and efficacy of this non-invasive X-ray induced luminescence
strategy in activating photo-agent in deep seated tumors.
Introduction: Photodynamic therapy (PDT) is a treatment for cancer requiring activation of a
photosensitizer for light-mediated tumor cytotoxicity. PDT is limited by tissue penetration because visible
light is required for photosensitizer activation. Sunstones<sup>TM</sup> are rare-earth phosphors which up-convert
energy from infrared wavelengths to emit higher energy in the visible spectrum. We utilized this unique
characteristic to generate light of appropriate intensity and wavelength for photosensitizer activation and
subsequent tumor cell eradication.
Methods: Sunstones<sup>TM</sup> with infrared absorption at 808 and 980nm and visible two-photon emission at
549.9 and 663.1nm were used. A murine NSCLC line was used to determine <i>in vitro </i>toxicity of
Sunstones<sup>TM</sup> and dose response curves for Sunstones<sup>TM</sup>-mediated PDT. Human NSCLC cells were
incubated with/without Photofrin<sup>TM</sup> (photosensitizer). Experimental groups included: Infrared light
treatment (IR), IR+Photofrin<sup>TM</sup>, IR+Sunstones<sup>TM</sup>, and IR+Sunstones<sup>TM</sup>+Photofrin<sup>TM</sup>. Groups were
exposed to 2.5W of 808nm light and assayed for metabolic activity.
Results: In vitro toxicity assays showed no significant toxicological side effects after 1 week incubation
with Sunstones<sup>TM</sup> and demonstrated linear response in cytotoxicity as treatment times and infrared dose
increased. IR+Sunstones<sup>TM</sup>+Photofri<sup>TM</sup> group showed significantly decreased metabolic activity
compared to control cells, cells treated with IR+Sunstones<sup>TM</sup>, and IR alone.
Conclusion: Sunstones<sup>TM</sup> are nontoxic nanocrystals capable of activating photosensitizers for PDT. Future
directions include conjugation of up-converters to a novel photosensitizer and managing the selective
uptake of conjugate by tumor cells.
Polystyrene dye doped plastic optical fiber was prepared and used to detect gamma and beta radiation from I<sub>151</sub> and TeO<sub>4</sub> gamma tracers typically used to get images of tumor areas within the human body. Absorption and fluorescence emission of TMQ, PBDBD365, POPOP styrene doped was performed under gamma and UV-irradiation. The fluorescence efficiency of the binary system PBDBD365-POPOP and the ternary TMQ- PBDBD365-POPOP was compared and according to the experimental results it was shown that the presence of the TMQ dye enhance the fluoresce obtained under I<SUB>151</SUB> radiation. Systematic characterization of the binary system was performed as function of primary dye concentration .
Photoluminescence (PL) of pure and 0.2 mol percent Sm<SUP>3+</SUP> doped zirconium oxide prepared by the Sol-Gel process and annealed at 1000 degrees C to stabilize the monoclinic phase were performed. The experimental spectra suggest the presence of energy transfer pro9cesses between the host and the dopant when the host was excited with a signal centered at 320 nm. The Sm<SUP>3+</SUP> doped monoclinic zirconium oxide shows strong emission at the green and red bands, corresponding to the <SUP>4</SUP>G<SUB>5/2</SUB> yields <SUP>6</SUP>H<SUB>5/2</SUB> and <SUP>4</SUP>G<SUB>5/2</SUB> yields <SUP>6</SUP>H<SUB>7/2</SUB> samarium transition, respectively; whereas the undoped sample only shows a broad band emission centered at 495 nm. The main mechanism that allows the samarium emission under UV-excitation appears to be non-radiative energy transfer from the ZoO<SUB>2</SUB> host to the Sm<SUP>3+</SUP> ions.
Spectroscopic properties of Nd<SUP>3+</SUP> in barium fluoroborophosphate and barium fluorosulphatephosphate glassy matrices have been analyzed by fitting the experimental data with the standard Judd-Ofelt theory. Various spectroscopic parameters viz. Radiative transition probabilities, radiative decay time, stimulated emission cross sections and quantum efficiency of the principal fluorescence transition from the <SUP>4</SUP>F<SUB>3/2</SUB> metastable level are obtained. Results show that addition of borate content to the fluorophosphate matrix will reduce the fluorescence spectral properties of Nd<SUP>3+</SUP>, whereas the influence of sulphate content is to improve the fluorescence spectral properties over a considerable extent. A comparison of the radiative properties of two hosts with that of fluorophosphate shows that the performance of the fluorosulphatephosphate matrix is superior and hence can be considered as possible candidate for solid state laser amplifiers.
Non linear optical response and reverse saturable absorption behavior of various rare earth phthalocyanines such as Nd, Eu, Sm and La in di-methyl formamide (DMF) solution were studied under high power Nd:YAG laser excitation. The size of the central metal atom of the Pc ring is found to considerably affect the nonlinear response of these systems. Excited state absorption cross sections of these systems are measured from the limiting characteristics. The SmHPc<SUB>2</SUB> system yields maximum value for absorption cross-section and its potential application in DMF as a suitable optical limiter is also discussed.
The mechanism of non-radiative energy transfer between Tb<SUP>3+</SUP> and Nd<SUP>3+</SUP> ions in fluorophosphate glass has been analyzed with the Forster-Dexter theory. Several/transfer parameters such as the transfer probability, transfer efficiency, critical transfer distance, and critical concentration have been evaluated by fitting the experimental fluorescence spectrum of those ions with that theory. The recorded emission spectrum of Tb<SUP>3+</SUP> with different Nd<SUP>3+</SUP> ion concentrations shows that the transfer process from the <SUP>5</SUP>D<SUB>4</SUB> state of Tb<SUP>3+</SUP> to the <SUP>4</SUP>G<SUB>5/2</SUB> state of Nd<SUP>3+</SUP> is driven predominantly by a dipole-dipole interaction. The effect of this energy transfer is to considerably enhance the optical gain of the <SUP>4</SUP>F<SUB>3/2</SUB> to <SUP>4</SUP>I<SUB>11/2</SUB> emission band of Nd<SUP>3+</SUP> ions. The reduction in optical gain at high activator concentrations is attributed to the concentration quenching in Nd<SUP>3+</SUP> ion pairs. In addition to this, the dependence of the J-O parameters, several radiative properties of Nd<SUP>3+</SUP> ions in the phosphate content as well as the nature of alkali content were also studied.
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