"Manganese Extraction" Strategy Enables Tumor-Sensitive Biodegradability and Theranostics of Nanoparticles.
"Manganese Extraction" Strategy Enables Tumor-Sensitive Biodegradability and Theranostics of Nanoparticles.
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DOI：
10.1021/jacs.6b04299
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发表时间：
2016-08
影响因子：
15
通讯作者：
Luodan Yu;Yu Chen;Meiying Wu;Xiaojun Cai;Heliang Yao;Linlin Zhang;Hangrong Chen;Jianlin Shi
中科院分区：
文献类型：
--
作者：
Luodan Yu;Yu Chen;Meiying Wu;Xiaojun Cai;Heliang Yao;Linlin Zhang;Hangrong Chen;Jianlin Shi
无机纳米颗粒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，一种新的“金属离子掺杂”的方法已被开发，赋予无机介孔二氧化硅为基础的纳米粒子与肿瘤敏感的生物降解和治疗诊断功能，简单地通过拓扑变换的介孔二氧化硅金属掺杂的复合纳米制剂。在锰掺杂的中空介孔二氧化硅纳米颗粒（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Si-O-Si键的断裂。Mn-HMSNs对肿瘤微环境的弱酸性和还原性敏感，生物降解速度快，能加速肿瘤药物的释放，增强肿瘤的T1加权成像。PEG化Mn-HMSNs介导的抗癌药物递送同时实现了高的肿瘤抑制效果，并且在体内系统地证明了复合纳米系统的高生物相容性。这是首次展示了对肿瘤微环境敏感的具有特定生物降解行为的可生物降解无机介孔纳米系统，也为简单地通过“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可行的途径，为解决无机药物载体的低生物降解性问题铺平了道路。
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.