Polymer nanoparticles for cancer-targeted drug delivery and nuclear imaging

Abstract

Nano-sized vesicular systems (nanoparticles), ranging from 10 nm to 1,000 nm in size, have potential applications in a wide variety of biomedical fields such as drug delivery systems, gene delivery systems, molecular imaging, and tissue engineering. For example, the development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. Here we describe various nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and investigate the mechanisms underlying the tumor targeting with nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of nanoparticles were influenced by several key factors i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, ii) particle size, iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.