The State Key Lab of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences , Shanghai 200050, P. R. China.
University of Chinese Academy of Sciences , Beijing 100049, P.R. China.
J Am Chem Soc. 2016 Aug 10;138(31):9881-94. doi: 10.1021/jacs.6b04299. Epub 2016 Aug 2.
Biodegradability of inorganic nanoparticles is one of the most critical issues in their further clinical translations. In this work, a novel "metal ion-doping" approach has been developed to endow inorganic mesoporous silica-based nanoparticles with tumor-sensitive biodegradation and theranostic functions, simply by topological transformation of mesoporous silica to metal-doped composite nanoformulations. "Manganese extraction" sensitive to tumor microenvironment was enabled in manganese-doped hollow mesoporous silica nanoparticles (designated as Mn-HMSNs) to fast promote the disintegration and biodegradation of Mn-HMSNs, further accelerating the breakage of Si-O-Si bonds within the framework. The fast biodegradation of Mn-HMSNs sensitive to mild acidic and reducing microenvironment of tumor resulted in much accelerated anticancer drug releasing and enhanced T1-weighted magnetic resonance imaging of tumor. A high tumor-inhibition effect was simultaneously achieved by anticancer drug delivery mediated by PEGylated Mn-HMSNs, and the high biocompatibility of composite nanosystems was systematically demonstrated in vivo. This is the first demonstration of biodegradable inorganic mesoporous nanosystems with specific biodegradation behavior sensitive to tumor microenvironment, which also provides a feasible approach to realize the on-demand biodegradation of inorganic nanomaterials simply by "metal ion-doping" strategy, paving the way to solve the critical low-biodegradation issue of inorganic drug carriers.
无机纳米粒子的生物降解性是其进一步临床转化的最关键问题之一。在这项工作中，开发了一种新颖的“金属离子掺杂”方法，通过介孔硅到金属掺杂复合纳米制剂的拓扑转化，赋予基于介孔硅的无机纳米粒子肿瘤敏感的生物降解性和治疗诊断功能。在锰掺杂的中空介孔硅纳米粒子（命名为 Mn-HMSNs）中实现了对肿瘤微环境敏感的“锰提取”，以快速促进 Mn-HMSNs 的崩解和生物降解，进一步加速框架内的 Si-O-Si 键断裂。Mn-HMSNs 对肿瘤微酸性和还原性环境的快速生物降解导致抗癌药物的释放大大加速，并增强了肿瘤的 T1 加权磁共振成像。通过 PEG 化 Mn-HMSNs 介导的抗癌药物递送同时实现了高肿瘤抑制效果，并且体内系统地证明了复合纳米系统的高生物相容性。这是首例具有肿瘤微环境敏感的特定生物降解行为的可生物降解无机介孔纳米系统的演示，也为通过“金属离子掺杂”策略实现无机纳米材料的按需生物降解提供了一种可行的方法，为解决无机药物载体的低生物降解性这一关键问题铺平了道路。
