Chen Xiaolu, Sun Hui, Hu Jun, Han Xia, Liu Honglai, Hu Ying
Key Laboratory for Advanced Materials and School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Key Laboratory for Advanced Materials and School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Colloids Surf B Biointerfaces. 2017 Apr 1;152:77-84. doi: 10.1016/j.colsurfb.2017.01.010. Epub 2017 Jan 8.
This work reports on a targeted and controlled drug delivery system based on protein decorated mesoporous silica nanoparticles (MSNs). In this system, transferrin (Tf), a naturally existing protein, is grafted on the surfaces of MSNs via redox-cleavable disulfide bonds, serving as both a capping agent and a targeting ligand simultaneously. The uniform particles with ordered mesoporous structures and the successful construction of the Tf/MSN hybrid nanocarriers can be confirmed through combined techniques. It is found that the model anticancer drug doxorubicin (DOX) can be efficiently encapsulated in the MSNs in the absence of glutathione (GSH), and a burst release of DOX is observed when the system is exposed to GSH, indicating good capping efficiency of Tf and redox-responsive release of DOX. Owing to the biocompatible Tf shell, the hybrid nanocarriers exhibited excellent biocompatibility in a wide concentration range and enhanced intracellular accumulation and targeting capability to tumor cells in vitro. The facile approach and the strategy of integration of multifunctions into one moiety present great potential in site-specific, controlled-release drug delivery system and provide us new ideas in design of MSN-based nanocontainers.
这项工作报道了一种基于蛋白质修饰的介孔二氧化硅纳米颗粒（MSNs）的靶向控释给药系统。在该系统中，天然存在的蛋白质转铁蛋白（Tf）通过可被氧化还原裂解的二硫键接枝在MSNs表面，同时作为封端剂和靶向配体。通过组合技术可以确认具有有序介孔结构的均匀颗粒以及Tf/MSN杂化纳米载体的成功构建。研究发现，在没有谷胱甘肽（GSH）的情况下，模型抗癌药物阿霉素（DOX）可以有效地封装在MSNs中，当该系统暴露于GSH时会观察到DOX的突发释放，这表明Tf具有良好的封端效率以及DOX的氧化还原响应释放特性。由于具有生物相容性的Tf外壳，杂化纳米载体在很宽的浓度范围内表现出优异的生物相容性，并在体外增强了对肿瘤细胞的细胞内积累和靶向能力。这种简便的方法以及将多种功能整合到一个部分的策略在定点控释给药系统中具有巨大潜力，并为基于MSN的纳米容器的设计提供了新的思路。
