文献名：A dual-sensitive mesoporous silica nanoparticle based drug carrier for cancer synergetic therapy 

作者：Jing Zhang, Biao Shen, Liqun Chen, Lingdong Chen, Yangsheng Meng, Jie Feng

College of Materials Science & Engineering, Zhejiang University of Technology, Hangzhou 310014, China

摘要：A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.