(547a) Multifunctional Rare-Earth Doped Nanoparticles in Encapsulated Albumin Nanocarriers for Tumor Targeting

Multifunctional drug probes that can track the delivery of and spatio-temporal responses to localized drugs in vivo can serve as powerful diagnostic tools for controlled targeting and therapies. The conventional use of visible-light, excitable fluorophore based probes is limited by poor tissue penetration and autofluorescence, while many inorganic nanoparticles such as quantum dots cause localized toxicity. We have developed a novel family of drug carrier probe nanoparticles that utilize "upconversion fluorescence", which is generated by the excitation of near infrared light and provides highly useful luminescence for biological imaging both in vitro and in vivo. Our approach involves fabrication of water dispersible, biologically targeted, Yb,Er co-doped NaYF4 nanoparticles (REs) by encapsulation in autofluorescent human serum albumin nanocarriers (RE-ANCs). Human serum albumin nanocarriers are biocompatible with many cell types over a large range or concentrations, taken up readily by cells, non-immunogenic, bind reversibly to hydrophobic substances and have numerous functional entities available for conjugating ligands and other moieties. Our nanocomposites can be tuned to have sizes between 75-275 nm, while exhibiting narrow polydispersity and high stability in aqueous solution for over 30 days. The albumin-encapsulation significantly reduced the cytotoxicity of the REs in vitro while providing surface amine groups for chemically conjugating targeting ligands. RE-ANCs modified with cyclic RGD rapidly targeted αVβ3 integrin receptors overexpressed on the U87 glioblastoma cells with minimal targeting of the low integrin expressing A172 cells. Furthermore, we have designed RE-ANCs for the in vitro and in vivo delivery of a metabotropic glutamate receptor 1 inhibitor, shown to suppress cell proliferation and trigger cell death in melanomas. Outcomes from our research can advance the design and interactions of multifunctional albumin particles as targetable and visualizable drug carriers both in vitro and in vivo .