Cooperative Dual-Activity Targeted Nanomedicine for Specific and Effective Prostate Cancer Therapy

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• 作者：Hung-Wei Yang ; Mu-Yi Hua ; Hao-Li Liu ; Rung-Ywan Tsai ; Cheng-Keng Chuang ; Po-Chun Chu ; Pei-Yi Wu ; Ying-Hsu Chang ; Heng-Chang Chuang ; Kai-Jie Yu ; See-Tong Pang
• 刊名：ACS Nano
• 出版年：2012
• 出版时间：February 28, 2012
• 年：2012
• 卷：6
• 期：2
• 页码：1795-1805
• 全文大小：747K
• 年卷期：v.6,no.2(February 28, 2012)
• ISSN：1936-086X

文摘

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 (NH₂-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 掳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.

Keywords:

dual-targeted nanomedicine; PSMA; anti-PSMA; magnetic targeting; prostate cancer therapy