Zhao Qinfu, Wang Shengyu, Yang Yang, Li Xian, Di Donghua, Zhang Chungang, Jiang Tongying, Wang Siling
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No. 77, Life One Road, DD port, Dalian 116600, PR China.
Mater Sci Eng C Mater Biol Appl. 2017 Sep 1;78:475-484. doi: 10.1016/j.msec.2017.04.059. Epub 2017 Apr 13.
In this work, a redox and enzyme dual-stimuli responsive drug delivery system (DDS) with tracking function (HMSN-SS-CD@HA) based on carbon dots capped hollow mesoporous silica nanoparticles (HMSN) has been developed for targeted drug delivery. The positively charged CD nanoparticles prepared by polyethylenimine (PEI) were grafted on the pore openings of HMSN through disulfide bonds and were used as "gatekeepers" to trap the drugs within the hollow cavity. The hyaluronic acid (HA), a natural polysaccharide, was further grafted on the surface of HMSN to realize targeted drug delivery, controlled drug release and improved the stability. Doxorubicin (DOX) was chosen as a model drug due to its wide clinical application. In vitro drug release profiles demonstrated that DOX-loaded HMSN-SS-CD@HA exhibited redox and enzyme dual-responsive drug release property. In addition, the prepared HMSN-SS-CD@HA exhibited excellent fluorescent properties and biocompatibility. Confocal laser scanning microscope (CLSM) and flow cytometry (FCM) illustrated that HMSN-SS-CD@HA exhibited a higher cellular uptake via the CD44 receptor-mediated endocytosis by CD44-receptor over-expressed A549 cells than NIH-3T3 (receptor-negative) cells, leading to higher cytotoxicity against A549 cells than NIH 3T3 cells. This work suggested an exploration of dual-stimuli responsive as well as real-time imaging targeted drug delivery system based on HMSN and the prepared HMSN-SS-CD@HA could be a promising platform for cancer therapy.
在本研究中，基于碳点包覆的中空介孔二氧化硅纳米粒子（HMSN）开发了一种具有跟踪功能的氧化还原和酶双刺激响应药物递送系统（DDS，即HMSN-SS-CD@HA）用于靶向药物递送。通过聚乙烯亚胺（PEI）制备的带正电荷的CD纳米粒子通过二硫键接枝在HMSN的孔口上，并用作“守门人”将药物捕获在中空腔内。透明质酸（HA），一种天然多糖，进一步接枝在HMSN表面以实现靶向药物递送、控制药物释放并提高稳定性。由于阿霉素（DOX）临床应用广泛，因此选择其作为模型药物。体外药物释放曲线表明，负载DOX的HMSN-SS-CD@HA具有氧化还原和酶双响应药物释放特性。此外，制备的HMSN-SS-CD@HA表现出优异的荧光性能和生物相容性。共聚焦激光扫描显微镜（CLSM）和流式细胞术（FCM）表明，HMSN-SS-CD@HA通过CD44受体介导的内吞作用在CD44受体过表达的A549细胞中比NIH-3T3（受体阴性）细胞具有更高的细胞摄取，导致对A549细胞的细胞毒性高于NIH 3T3细胞。这项工作为基于HMSN的双刺激响应以及实时成像靶向药物递送系统的探索提供了思路，并且制备的HMSN-SS-CD@HA可能是一种有前景的癌症治疗平台。
