H-W YangM-Y HuaH-L LiuR-Y TsaiC-K ChuangP-C ChuP-Y WuY-H ChangH-C ChuangK-J YuS-T PangHAO-LI LIUH-W YangM-Y HuaH-L LiuR-Y TsaiC-K ChuangP-C ChuP-Y WuY-H ChangH-C ChuangK-J YuS-T Pang劉浩澧2020-10-072020-10-07201219360851https://scholars.lib.ntu.edu.tw/handle/123456789/516649A 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.[SDGs]SDG3journal article10.1021/nn20485262-s2.0-84857735087