Cooperative Dual-Activity Targeted Nanomedicine for Specific and Effective Prostate Cancer Therapy
| Autor: | Heng-Chang Chuang, Mu-Yi Hua, Hung-Wei Yang, Pei-Yi Wu, Rung-Ywan Tsai, Cheng-Keng Chuang, Kai-Jie Yu, See-Tong Pang, Po-Chun Chu, Ying-Hsu Chang, Hao-Li Liu |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Drug Paclitaxel Antibodies Neoplasm media_common.quotation_subject Contrast Media General Physics and Astronomy Antineoplastic Agents Pharmacology Polyethylene Glycols Mice Prostate cancer chemistry.chemical_compound Cell Line Tumor medicine Animals Humans General Materials Science Molecular Targeted Therapy media_common Drug Carriers biology Chemistry General Engineering Prostatic Neoplasms Cancer Prostate-Specific Antigen medicine.disease Magnetic Resonance Imaging Xenograft Model Antitumor Assays Tumor Burden Nanomedicine Cancer cell Magnets biology.protein Antibody Nanocarriers |
| Zdroj: | ACS Nano. 6:1795-1805 |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/nn2048526 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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