Xiao Dong, Jia Hui-Zhen, Ma Ning, Zhuo Ren-Xi, Zhang Xian-Zheng
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
Nanoscale. 2015 Jun 14;7(22):10071-7. doi: 10.1039/c5nr02247a. Epub 2015 May 15.
A redox-responsive mesoporous silica nanoparticle (RRMSN) was developed as a drug nanocarrier by noncovalent functionalization of MSNs with amphiphilic peptides containing the RGD ligand. The alkyl chain stearic acid (C18) with a thiol terminal group was anchored on the surface of MSNs via a disulfide bond, and the amphiphilic peptide (AP) C18-DSDSDSDSRGDS was coated by self-assembly through hydrophobic interactions between the octadecyl groups of MSNs and alkyl chains of AP, which played the role of a gatekeeper collectively. In vitro drug release profiles demonstrated that the anticancer drug (DOX) could be entrapped with nearly no leakage in the absence of dithiothreitol (DTT) or glutathione (GSH). With the addition of DTT or GSH, the entrapped drug released quickly due to the cleavage of the disulfide bond. It was found that after the internalization of MSNs by cancer cells via the receptor-mediated endocytosis, the surface amphiphilic peptides and alkyl chain of RRMSN/DOX were removed to induce rapid drug release intracellularly after the cleavage of the disulfide bond, triggered by GSH secreted in cancer cells. This novel intelligent RRMSN/DOX drug delivery system using self-assembly of amphiphilic peptides around the MSNs provides a facile, but effective strategy for the design and development of smart drug delivery for cancer therapy.
通过将含RGD配体的两亲性肽与介孔二氧化硅纳米颗粒（MSN）进行非共价功能化，开发了一种氧化还原响应性介孔二氧化硅纳米颗粒（RRMSN）作为药物纳米载体。带有硫醇端基的烷基链硬脂酸（C18）通过二硫键锚定在MSN表面，两亲性肽（AP）C18-DSDSDSDSRGDS通过MSN的十八烷基与AP的烷基链之间的疏水相互作用自组装包覆，二者共同起到了守门人的作用。体外药物释放曲线表明，在不存在二硫苏糖醇（DTT）或谷胱甘肽（GSH）的情况下，抗癌药物（阿霉素，DOX）几乎无泄漏地被包封。加入DTT或GSH后，由于二硫键的断裂，包封的药物迅速释放。研究发现，癌细胞通过受体介导的内吞作用内化MSN后，癌细胞分泌的GSH触发二硫键断裂，RRMSN/DOX的表面两亲性肽和烷基链被去除，从而在细胞内诱导药物快速释放。这种利用两亲性肽在MSN周围自组装的新型智能RRMSN/DOX药物递送系统，为癌症治疗的智能药物递送设计与开发提供了一种简便而有效的策略。
