A pH-sensitive prodrug strategy to co-deliver DOX and TOS in TPGS nanomicelles for tumor therapy

Publication date: 1 January 2019Source: Colloids and Surfaces B: Biointerfaces, Volume 173Author(s): Shujuan Xiong, Zhe Wang, Juan Liu, Xiangping Deng, Runde Xiong, Xuan Cao, Zhizhong Xie, Xiaoyong Lei, Yanming Chen, Guotao TangAbstractThis work has presented a novel strategy for designing pH-sensitive TOS-H-DOX prodrug-loaded TPGS nanomicelles for co-delivery TOS and DOX to enhance tumor therapy and reduce the toxic side effects. DOX was covalently conjugated to the vitamin E succinate through hydrazone bond to produce an pH-sensitive prodrug TOS-H-DOX (amido bond as a control, TOS-A-DOX), which was responsive to the acidic environment in tumor cells, and the prodrugs were subsequently encapsulated in the core of TPGS nanomicelles via hydrophobic effects with a significant drug loading capacity. The pH-sensitive prodrug nanomicelles TOS-H-DOX/TPGS exhibited potent release of DOX in acidic media relative to the pH-insensitive prodrug nanomicelles TOS-A-DOX/TPGS, and further studies of their intracellular uptake and intracellular localization demonstrated that TOS-H-DOX/TPGS nanomicelles can be effectively taken up by cells and drugs can be released. In vitro results confirmed that TOS-H-DOX/TPGS nanomicelles exhibited significant antitumor cell proliferation activity compared to TOS-A-DOX/TPGS and free DOX, TPGS. Furthermore, in vivo studies further confirmed an excellent synergistic antitumor efficacy in MCF-7 tumor-bearing nude mice model. More importantly, the H&E staining...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research