Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells

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• 作者：Xinxin Zhang ; Feifei Li ; Shiyan Guo ; Xi Chen ; Xiaoli Wang ; Juan Li ; Yong Gan
• 关键词：Multidrug resistance ; Mesoporous silica nanoparticle ; Triggered release ; Irinotecan ; Breast cancer resistance protein
• 刊名：Biomaterials
• 出版年：April, 2014
• 年：2014
• 卷：35
• 期：11
• 页码：3650-3665
• 全文大小：6003 K

文摘

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. A polymer-lipid supported mesoporous silica nanoparticle (PLS-MSNs) is described here to facilitate intracellular delivery of anticancer drug and enhance the antitumor efficacy against MDR breast cancer cells. By coating MSNs with a synthetic dual-functional polymer-lipid material P123-DOPE, the supported membrane acted as an intact barrier against the escape of encapsulated drugs before reaching the target cells, leading to depolymerization and triggered storm release of loaded irinotecan (CPT-11) in acidic endosomal pH of tumor cells. In addition, P123-DOPE can inhibit breast cancer resistance protein (BCPR) mediated CPT-11 efflux in drug resistant MCF-7/BCRP breast cancer cells, thus acting as a 鈥渄oor blocker鈥? Compared to free CPT-11, PLS-MSNs resulted in a maximum increase in the intracellular CPT-11 concentration (12.9-fold), had 7.1-fold higher cytotoxicity and processed a stronger cell cycle arrest in MCF-7/BCRP cells. Moreover, CPT-11 loaded PLS-MSNs showed high therapeutic performance and low toxicity in BALB/c nude mice bearing drug resistant breast tumors, with an inhibition rate of 81.2% compared to free CPT-11 treatment group. The reported PLS-MSNs provide promising applicability in future preclinical and clinical MDR cancer treatment.