Biomaterials. 2012 May;33(15):3919-30. Epub 2012 Feb 26. Yang HW, Hua MY, Liu HL, Tsai RY, Pang ST, Hsu PH, Tang HJ, Yen TC, Chuang CK. Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC.
Abstract Multidrug resistance (MDR) presents a major obstacle to curing cancer. Chemotherapy failure can occur through both cell membrane drug resistance (CMDR) and nuclear drug resistance (NDR), and anticancer effectiveness of chemotherapeutic agents is especially reduced by their nuclear export. Here we report an exciting magnetically-targeted nanomedicine formed by conjugation of epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC). Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides, the half-life of drug is prolonged ?1.8-fold (from 45 h to 81 h) at 37 °C, with a ?10-fold increase in concentration at the tumor site through magnetic targeting (MT). Moreover, malignant NDR bladder cancer can be effectively inhibited after 14 days in mice by just two injections and MT. We are the first to demonstrate the nanomedical strategy that can overcome the CMDR and NDR bladder cancers simultaneously, and proceed to the excellent MT therapy, significantly reducing the dosage and cardiotoxicity and holding great promise for incurable human MDR bladder cancer.
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