Nanoscale Coordination Polymers Codeliver Chemotherapeutics and siRNAs to Eradicate Tumors of Cisplatin-Resistant Ovarian Cancer

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• 作者：Chunbai He ; Christopher Poon ; Christina Chan ; S. Diane Yamada ; Wenbin Lin
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：May 11, 2016
• 年：2016
• 卷：138
• 期：18
• 页码：6010-6019
• 全文大小：533K
• 年卷期：0
• ISSN：1520-5126

文摘

Drug resistance impedes the successful treatment of many types of cancers, especially ovarian cancer (OCa). To counter this problem, we developed novel long-circulating, self-assembled core–shell nanoscale coordination polymer (NCP) nanoparticles that efficiently deliver multiple therapeutics with different mechanisms of action to enhance synergistic therapeutic effects. These NCP particles contain high payloads of chemotherapeutics cisplatin or cisplatin plus gemcitabine in the core and pooled siRNAs that target multidrug resistant (MDR) genes in the shell. The NCP particles possess efficient endosomal escape via a novel carbon dioxide release mechanism without compromising the neutral surface charge required for long blood circulation and effectively downregulate MDR gene expression in vivo to enhance chemotherapeutic efficacy by several orders of magnitude. Even at low doses, intraperitoneal injections of nanoparticles led to effective and long-lasting tumor regression/eradication in subcutaneous and intraperitoneal xenograft mouse models of cisplatin-resistant OCa. By silencing MDR genes in tumors, self-assembled core–shell nanoparticles promise a more effective chemotherapeutic treatment for many challenging cancers.