Near infrared labeling of PLGA for in vivo imaging of nanoparticles

To introduce optical imaging among methods available to follow nanoparticle biodistribution, we have evaluated the concept of covalently labeling poly(lactide-co-glycolide) (PLGA) with a near-infrared (NIR) dye to obtain stable NIR fluorescent nanoparticles. PLGA was coupled with the NIR dye (DY-700, Dyomics) by an amide bond with 38% efficiency. Incorporating 1% of this conjugate into PLGA nanoparticles stabilised by polyvinyl alcohol (PVA) leads to stable nanoparticles (NPs) without affecting their colloidal characteristics (average diameter, polydispersity and zeta potential). In addition, nanoparticles remain strongly fluorescent and display good storage stability for 4 weeks at 4 °C or over one week at 37 °C. Nanoparticle cytotoxicity evaluated using HUVEC, NIH/3T3 and J774.A1 cell lines was similar for unlabeled or labeled NPs. Fluorescent nanoparticles and free dye were injected intravenously into mice and their biodistribution was followed for 24 h by NIR imaging, in vivo and ex vivo. Nanoparticles were found mainly in the liver whereas the free dye was not accumulating preferentially in this organ. The DY-700 NIR conjugate incorporated into PLGA NPs shows good performance both in vitro and in vivo, thus paving the way to finely traceable PLGA nanosystems for in vivo administration.