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

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成果类型:
期刊论文
作者:
ShujuanXiong;ZheWang;JuanLiu;XiangpingDeng;RundeXiong;XuanCao;ZhizhongXie;XiaoyongLei;YanmingChen;GuotaoTang
通讯作者:
Tang, Guotao
作者机构:
[ZheWang; XiangpingDeng; ZhizhongXie; JuanLiu; XiaoyongLei; ShujuanXiong; RundeXiong; XuanCao] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
[YanmingChen] Jiuzhitang Co., Ltd, China
[ShujuanXiong] The People's Hospital of Yiyang, China
[GuotaoTang] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. Electronic address: tgtzq@163.com
通讯机构:
[Tang, Guotao] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. Electronic address:
语种:
英文
关键词:
pH-sensitive;Prodrug;Co-delivery;Tumor therapy;Low toxicity
期刊:
Colloids and surfaces. B, Biointerfaces
ISSN:
0927-7765
年:
2019
卷:
173
页码:
346-355
入藏号:
PMID:30316081
机构署名:
本校为第一且通讯机构
院系归属:
药学与生物科学学院
摘要:
This 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 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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