State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China; School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Biomaterials. 2018 May;163:1-13. doi: 10.1016/j.biomaterials.2018.02.018. Epub 2018 Feb 9.
Inorganic mesoporous silica-based nanovehicles are highly promising for drug delivery but still suffer from the disadvantages of lacking functionality and poor biodegradability on account of the inert silica framework. Moreover, conventional cancer therapeutics typically employ toxic anticancer drugs or invasive external irradiations, which will inevitably give rise to severe adverse effects and diminished therapeutic outcome. In this work, we report on the iron engineered framework of mesoporous silica nanoparticles (MSNs) to fabricate a nanocatalyst with biodegradable and catalytic framework via a "dissolution-regeneration" strategy (designated as rFeO-HMSN). Based on the abundant overexpressed hydrogen peroxide (HO) and mild acidic nature in tumor microenvironment (TME), rFeO-HMSN nanocatalyst could trigger in-situ Fenton-like reactions to produce highly toxic hydroxyl radicals (·OH), causing remarkable oxidative damages against tumor cells/xenografts. Additionally, the iron-engineered rFeO-HMSN nanocatalyst could readily collapse via an iron-extraction strategy under protein-rich environment, thereby improving the biodegradability of rFeO-HMSN nanocatalyst. This work paves a promising way to engineer the inert framework of MSN into functional, biodegradable and catalytic nanoplatform, featuring effective tumor-therapeutic outcome and stimuli-responsive biodegradation concurrently.
基于介孔硅的无机纳米载体在药物传递方面具有很大的应用前景，但由于惰性的硅骨架，它们仍然存在缺乏功能和生物降解性差的缺点。此外，传统的癌症治疗方法通常采用有毒的抗癌药物或侵入性的外部辐射，这不可避免地会导致严重的副作用和治疗效果降低。在这项工作中，我们报告了介孔硅纳米粒子（MSNs）的铁工程框架，通过“溶解-再生”策略（命名为 rFeO-HMSN）来构建具有生物可降解和催化框架的纳米催化剂。基于肿瘤微环境（TME）中丰富的过表达过氧化氢（HO）和温和的酸性，rFeO-HMSN 纳米催化剂可以引发原位类芬顿反应，产生高毒性的羟基自由基（·OH），对肿瘤细胞/异种移植物造成显著的氧化损伤。此外，铁工程 rFeO-HMSN 纳米催化剂可以在富含蛋白质的环境下通过铁提取策略轻易崩溃，从而提高 rFeO-HMSN 纳米催化剂的生物降解性。这项工作为将 MSN 的惰性框架设计成具有功能、生物可降解和催化的纳米平台铺平了道路，具有有效的肿瘤治疗效果和对刺激的响应性生物降解。
