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.
Written by:
Yang HW, Hua MY, Liu HL, Tsai RY, Chuang CK, Chu PC, Wu PY, Chang YH, Chuang HC, Yu KJ, Pang ST. Are you the author?
Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan 33302, Taiwan R.O.C.
Reference: ACS Nano. 2012 Feb 28;6(2):1795-805. Epub 2012 Jan 24.
PubMed Abstract
PMID: 22248493
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