期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 173, 期 -, 页码 346-355出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2018.10.012
关键词
pH-sensitive; Prodrug; Co-delivery; Tumor therapy; Low toxicity
资金
- open fund project for innovation platform of universities in Hunan [17K082]
- Construct Program of the Key Discipline in Hunan province
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study
This work has presented a novel strategy for designing pH-sensitive TOS-H-DOX prodrug-loaded TPGS nano micelles 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 of the heart, liver, kidney tissue sections of experimental nude mice showed that TOS-H-DOX/TPGS nanomicelles can reduce damage to them.
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