Nanosomal Microassemblies for Highly Efficient and Safe Delivery of Therapeutic Enzymes

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• 作者：Huarong Xiong ; Yunli Zhou ; Qixin Zhou ; Dan He ; Shengli Wan ; Qunyou Tan ; Mi Zhang ; Xue Deng ; Jingqing Zhang
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：September 16, 2015
• 年：2015
• 卷：7
• 期：36
• 页码：20255-20263
• 全文大小：683K
• ISSN：1944-8252

文摘

Enzyme therapy has unique advantages over traditional chemotherapies for the treatment of hyperuricemia, but overcoming the delivery obstacles of therapeutic enzymes is still a significant challenge. Here, we report a novel and superior system to effectively and safely deliver therapeutic enzymes. Nanosomal microassemblies loaded with uricase (NSU-MAs) are assembled with many individual nanosomes. Each nanosome contains uricase within the alkaline environment, which is beneficial for its catalytic reactions and keeps the uricase separate from the bloodstream to retain its high activity. Compared to free uricase, NSU-MAs exhibited much higher catalytic activity under physiological conditions and when subjected to different temperatures, pH values and trypsin. NSU-MAs displayed increased circulation time, improved bioavailability, and enhanced uric acid-lowering efficacy, while decreasing the immunogenicity. We also described the possible favorable conformational changes occurring in NSU-MAs that result in favorable outcomes. Thus, nanosomal microassemblies could serve as a valuable tool in constructing delivery systems for therapeutic enzymes that treat various diseases.