State Laboratory 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.
Small. 2018 Aug;14(35):e1800708. doi: 10.1002/smll.201800708. Epub 2018 Aug 1.
Inorganic nanocarriers have shown their high performance in disease theranostics in preclinical animal models and further great prospects for clinical translation. However, their dissatisfactory biodegradability and pre-drug leakage with nonspecificity to lesion sites significantly hinders the possible clinical translation. To solve these two critical issues, a framework-engineering strategy is introduced to simultaneously achieve enhanced biodegradability and controllable drug releasing, based on the mostly explored mesoporous silica-based nanosystems. The framework of mesoporous silica is engineered by direct Mg doping via a generic dissolution and regrowth approach, and it can transform into the easy biodegradation of magnesium silicate nanocarriers with simultaneous on-demand drug release. Such magnesium silicate nanocarriers can respond to the mild acidic environment of tumor tissue, causing the fast breaking up and biodegradation of the silica framework. More interesting, the released Mg can further activate Mg -dependent DNAzyme on the surface of hollow mesoporous magnesium silicate nanoparticles (HMMSNs) to cleave the RNA-based gatekeeper, which further accelerates the release of loaded anticancer drugs. Therefore, enhanced anticancer efficiency of chemotherapeutic drugs assisted by the biodegradable intelligent HMMSNs is achieved. The high biocompatibility of nanocarriers and biodegradation products is demonstrated and can be easily excreted via feces and urine guaranteeing their further clinical translation.
无机纳米载体在临床前动物模型中的疾病治疗学方面表现出了优异的性能，并且具有进一步向临床转化的巨大前景。然而，它们较差的生物降解性和非特异性对病变部位的预药物泄漏，严重阻碍了其可能的临床转化。为了解决这两个关键问题，我们引入了一种框架工程策略，基于探索最多的介孔硅基纳米系统，同时实现增强的生物降解性和可控的药物释放。介孔硅的框架通过通用的溶解和再生长方法直接进行 Mg 掺杂来进行工程化处理，可转化为易于生物降解的硅酸镁纳米载体，同时实现按需药物释放。这种硅酸镁纳米载体可以响应肿瘤组织的温和酸性环境，导致硅框架快速分解和生物降解。更有趣的是，释放的 Mg 可以进一步激活空心介孔硅酸镁纳米粒子（HMMSNs）表面的 Mg 依赖性 DNA 酶，切割基于 RNA 的门控分子，从而进一步加速负载抗癌药物的释放。因此，可生物降解的智能 HMMSNs 增强了化疗药物的抗癌效率。纳米载体和降解产物的高生物相容性得到了证明，它们可以通过粪便和尿液轻松排出，保证了它们的进一步临床转化。
