Polymer inhibitors of ABC transporter overcoming multidrug resistance: synthesis,characterization an

来源 :The Third Symposium on Innovative Polymers for Controlled De | 被引量 : 0次 | 上传用户:lingliang416
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  One of the most significant problems of chemotherapy is that even originally very sensitive tumors become often resistant to cytostatic after several cycles of treatment.This so-called multidrug resistance (MDR) phenomenon is caused by the over-expression of the MDR gene-encoded proteins,e.g.P-glycoprotein (P-gp),an ATP-dependent exporter which increases the efflux of anticancer drugs from cancer cells [1].Two P-gp inhibitors of ABC transporters,reversin 121 (Boc-Asp(OBzl)-Lys(Z)-OtBu) and ritonavir which are able to restore the cytotoxicity of anticancer drugs in MDR cells,were used in this study.The aim of this work was to synthesize water-soluble polymer conjugates based on N-(2-hydroxypropyl)methacrylamide copolymers (pHPMA) containing either inhibitor of ABC transporters,anticancer drug doxorubicin (DO)X) or both.These conjugates due to theit prolonged blood circulation and passive accumulation in tumor tissue (EPR effect) can improve the efficacy of anticancer drugs and overcome nonspecific side effects on healthy tissue [2].
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