Fluorescence is a very promising radioactive-free technique for functional imaging in small animals and, in the future, in humans. However, most commercial near-infrared dyes display poor optical properties, such as low fluorescence quantum yields and short fluorescence lifetimes. In this paper, we explore whether the encapsulation of infrared cyanine dyes within the core of lipid nanoparticles (LNPs) could improve their optical properties. Lipophilic dialkylcarbocyanines DiD and DiR are loaded very efficiently in 30-35-nm-diam lipid droplets stabilized in water by surfactants. No significant fluorescence autoquenching is observed up to 53 dyes per particle. Encapsulated in LNP, which are stable for more than one year at room temperature in HBS buffer (HEPES 0.02 M, EDTA 0.01 M, pH 5.5), DiD and DiR display far improved fluorescence quantum yields (respectively, 0.38 and 0.25) and longer fluorescence lifetimes (respectively, 1.8 and 1.1 ns) in comparison to their hydrophilic counterparts Cy5 (=0.28, =1.0 ns) and Cy7 (=0.13, =0.57 ns). Moreover, dye-loaded LNPs are able to accumulate passively in various subcutaneous tumors in mice, thanks to the enhanced permeability and retention effect. These new fluorescent nanoparticles therefore appear as very promising labels for in vivo fluorescence imaging.
Fluorescence imaging (FLI) allows the in vivo monitoring of biological events associated with disease and
represents a new promising tool for drug discovery. In particular, it speeds up the development and assessment of new
therapies in oncology, helps in diagnosis, and improves surgery by fluorescence-guided tumor resection. This technique
is highly sensitive, non-ionizing, easy to use and relatively inexpensive.
Nevertheless, the main limitation of FLI lies in the optical properties of biological tissues. Mainly because of
haemoglobin and water absorption, only near-infrared (NIR) light is adapted to image tissues in depth. Using a
contrasting agent absorbing and emitting in the NIR region is therefore necessary to improve the background signal ratio,
and thus the image contrast.
Among many commercially available NIR optical contrast agents, only indocyanine green (ICG), has been
approved by the United State Food and Drug Administration (FDA) for various medical applications. However, its
instability (photo-degradation, thermal-degradation and low aqueous solubility) limits its applications as a fluorescent
probe for imaging purposes. In order to improve the effectiveness of ICG, we engineered ICG-doped lipid nanoparticles
In this communication, we will report the design of these novel fluorescent nanoparticle probes. These low cost
nanocarriers have numerous advantages, including their high chemical stability and biocompatibility. The
characterization of the optical properties of the nanoparticles entrapping ICG will also be discussed. Finally, the
biodistribution in mice of ICG when delivered through nanoparticles in comparison to free ICG in solution is presented.
It demonstrates the efficient accumulation of ICG-doped nanoparticles in the tumor site.