【作者】 谢萌； 龚艳容； 金一；

【Author】 Meng Xie,Cheng Run Wang,Yan Rong Gong,Yi Jin (Institute of Pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University)

【机构】 浙江大学药学院药物制剂研究所；

【摘要】 药物耐受是导致肿瘤化疗失败的主要因素,其中药物多药耐受转运体糖蛋白(P-glycoprotein,P-gp)的过度表达是造成肿瘤多药耐药的最主要机制,也是逆转多药耐药的最主要靶点。通过抑制或调节转运体蛋白的活性,从而增加药物在靶组织的有效浓度,是提高药物对肿瘤治疗效果的一项重要措施。为了研究纳米制剂对P糖蛋白介导多药耐药的逆转作用,本研究合成了具有较大载药量的羧基功能化介孔二氧化硅纳米粒,并研究了给药系统的体外释放、细胞毒性及细胞摄取行为。研究结果显示空白载体对细胞的毒性很小,具有良好的生物相容性。药物的释放具有明显的pH依赖性,在pH5.0的介质中有最佳的释放行为。载药纳米粒对人乳腺癌细胞耐药株的逆转作用是游离阿霉素的6倍,而对敏感株的毒性作用与游离药物相似。提示该纳米粒在肿瘤治疗领域具有潜在应用价值。更多还原

【Abstract】 Drug resistance is a major obstacle to the success of cancer chemotherapy.Overexpression of the drug-efflux transporter P-glycoprotein(P-gp) is a key factor contributing to tumor drug resistance.One strategy to enhance the therapeutic efficacy of drugs against cancer is to increase their available concentrations at the target site by suppressing or modulating efflux-transporters.To test the ability of nanoparticle formulations to overcome P-glycoprotein(P-gp)-mediated multidrug resistance,carboxyl functionalized MSN(MSN/COOH) with high loading capacity were prepared.Blank nanoparticles exhibited low cytotoxicity and the drug delivery system had a desirable release-acceleration pH(pH5.0) for cytoplasmic drug delivery.Most importantly,Doxorubicin nanoparticles showed 20-fold lower IC 50 values in P-gp-overexpressing human cancer cells than those of free doxorubicin,indicating that the drug resistance of NCI-ADR/RES cells was significantly reversed via the interaction between nanoparticle and P-gp.Therefore,this type of nanoparticle has potential superiority for cancer therapy.更多还原