Original Article Nanoparticle mediated chemotherapy of hormone refractory prostate cancer with a novel combi-molecule

* Equal contributors. Received June 13, 2015; Accepted July 31, 2015; Epub August 15, 2015; Published August 30, 2015 Abstract: In previous study, we synthesized a novel combi-molecule, JDF-12, with superior cytotoxicity against pros- tate cancer cells, but it has a poor stability in liquid after preparation with traditional method and is susceptible to hydrolysis and binding to organs highly expressing epidermal growth factor receptor (EGFR), resulting in side effects. In this study, the nanotechnology was employed to prepare JDF-12 aiming to increase its anti-tumor effect and reduce its systemic side effects. The JDF-12 loaded nanoparticles were formulated with biocompatible and biodegradable poly (D,L-lactic-co-glycolic acid)-block-poly(ethyleneglycol) (PLGA-b-PEG) copolymer and surface func- tionalized with a single-chain antibody that recognizes the extracellular domain of prostate stem cell antigen (PSCA), enabling a controlled release, "stealth" property, and cell-specific targeting. The targeted nanoparticles exhibited a sustained drug release in vitro and were specifically endocytosed by prostate cancer cells though the receptor- mediated endocytosis resulting in enhanced cellular toxicity in vitro. Moreover, a better outcome with reduced drug toxicity was observed in a PC3M xenograft animal model after treatment with these nanoparticles. Our results demonstrate the feasibility of nanoparticle-based technology in the development of pharmaceutically suboptimal chemotherapeutics.