title: Nanoparticle mediated chemotherapy of hormone refractory prostate cancer with a novel combi-molecule.
abstract: In previous study, we synthesized a novel combi-molecule, JDF-12, with superior cytotoxicity against prostate 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 functionalized 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.
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, China.
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Fang
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, China.
authors.forename: Jie-Ying
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, China.
authors.forename: Teng-Cheng
authors.initials: TC
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Urology, Affiliated Hospital of Guilin Medical College Guilin 541004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
keywords: Prostate cancer; epidermal growth factor receptor; nanoparticle