title: Cooperative dual-activity targeted nanomedicine for specific and effective prostate cancer therapy.
abstract: A key issue in cancer therapy is how to enhance the tumor-targeting efficacy of chemotherapeutic agents. In this study, we developed a cooperative dual-targeted delivery platform for paclitaxel (PTX) that has potential application as a powerful prostate cancer treatment. The nanomedicine was prepared by first conjugating PTX to nontoxic high-magnetization nanocarriers which can be actively guided and targeted by an external magnet. Next, the surface was functionalized with carboxylated o-(2-aminoethyl)polyethyleneglycol (NH(2)-EPEG-COOH) to enable uptake by the reticuloendothelial system. Antiprostate-specific membrane antigen antibodies (APSMAs) were then conjugated onto the carrier to recognize the extracellular domain of the prostate-cancer specific membrane antigen (PSMA), thus binding to cancer cells as a secondary active targeting mechanism. We found a significant enhancement of PTX concentration at the tumor site by nearly 20-fold. In addition, the drug half-life was prolonged more than 4.1-fold (from 24 to 99 h) at 37 °C. Low-dose (4.5 mg/kg) injection of the dual-targeted therapeutic nanomedicine in the presence of magnetic targeting significantly prolonged the median survival of nude mice from 35 to 58 days compared to mice that received a high dose (6 mg/kg) of free PTX. This report demonstrates the potential utility of targeted nanomedicine in the clinical treatment of cancer.
authors.affiliation: Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan 33302, Taiwan R.O.C.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Mu-Yi
authors.initials: MY
authors.lastname: Hua
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Rung-Ywan
authors.initials: RY
authors.lastname: Tsai
authors.forename: Cheng-Keng
authors.initials: CK
authors.lastname: Chuang
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chu
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Wu
authors.forename: Ying-Hsu
authors.initials: YH
authors.lastname: Chang
authors.forename: Heng-Chang
authors.initials: HC
authors.lastname: Chuang
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Yu
authors.forename: See-Tong
authors.initials: ST
authors.lastname: Pang
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003287:Contrast Media; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D059346:Magnets / Q000737:chemistry; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D050997:Nanomedicine / Q000379:methods*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D011092:Polyethylene Glycols; D017430:Prostate-Specific Antigen; D017239:Paclitaxel