Zhang Linlin, Wang Liying, Yao Heliang, Xu Fangfang, Chen Yu
State Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.
J Mater Chem B. 2017 Oct 21;5(39):8013-8025. doi: 10.1039/c7tb01526g. Epub 2017 Oct 2.
The construction of large pore-sized hollow mesoporous organosilica nanoparticles (HMONs) with a concurrent small particle size is of great challenge for the delivery of large biomacromolecules. In this work, we report, for the first time, on the construction of monodispersed and biodegradable HMONs with a unique large mesopore size, hollow interior, a small particle size and a molecularly organic-inorganic hybrid framework. The incorporation of thioether groups into the framework of large pore-sized HMONs (LHMONs) leads to the fast biodegradation of the nanocarriers with specific responsibility and acceleration to the reducing microenvironment. Systematic in vivo biocompatibility assays of LHMONs demonstrate their high biosafety for potential clinical translation. Based on their large mesopore and high pore volume, these LHMONs show high drug-loading capacity for large biomolecular proteins (RNase A), efficient intracellular uptake and a high therapeutic outcome against cancer cells as compared to free protein drugs because of their unique structural features. This first demonstration of the construction of molecularly organic-inorganic hybrid HMONs with a unique large mesopore size, a small particle size and tumor microenvironment-responsive biodegradability promises the intracellular delivery of biomacromolecules for various therapeutic applications, especially for combating cancer.
构建同时具有小粒径的大孔径中空介孔有机硅纳米粒子（HMONs）对于递送大型生物大分子而言极具挑战。在这项工作中，我们首次报道了构建具有独特大介孔尺寸、中空内部、小粒径以及分子有机-无机杂化骨架的单分散且可生物降解的HMONs。将硫醚基团引入大孔径HMONs（LHMONs）的骨架中，可使纳米载体快速生物降解，并对特定的还原微环境具有加速作用。对LHMONs进行的系统体内生物相容性分析表明其具有较高的生物安全性，有望用于临床转化。基于其大介孔和高孔体积，这些LHMONs对大型生物分子蛋白（核糖核酸酶A）显示出高载药能力、高效的细胞内摄取以及与游离蛋白药物相比更高的抗癌细胞治疗效果，这归因于其独特的结构特征。首次构建出具有独特大介孔尺寸、小粒径以及肿瘤微环境响应性生物降解性的分子有机-无机杂化HMONs，有望实现生物大分子在细胞内的递送，用于各种治疗应用，尤其是抗癌治疗。
