Enzyme-activatable disk-shaped nanocarriers augment tumor permeability for breast cancer combination therapy  

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作  者:Hanming Zhang Honglin Gao Yicong Zhang Yikun Han Qing Lin Tao Gong Xun Sun Zhirong Zhang Ling Zhang Shiqi Huang 

机构地区:[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [2]Med-X Center for Materials,College of Polymer Science and Engineering,Sichuan University,Chengdu 610065,China

出  处:《Nano Research》2024年第7期6400-6410,共11页纳米研究(英文版)

基  金:The Regional Innovation and Development Joint Fund(No.U20A20411);the National Science Fund for Excellent Young Scholars(No.82022070)provided funding for this work。

摘  要:Unique physiopathological characteristics of tumor tissues impose obstacles to the sufficient penetration of traditional nanomedicines,resulting in undesirable drug delivery efficacy and therapeutic outcomes.Here,we constructed TRAIL-[NDHCPT]^(GAC),a synergistic hydroxycamptothecin(HCPT)and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)protein co-loaded disk-shaped nanocarrier withγ-glutamyl transpeptidase responsiveness.When the novel nanodisks extravasated into the tumor interstitium,theγ-glutamyl transpeptidase overexpressed on the tumor cell membranes cleaved theγ-glutamyl portions of the nanodisk surface to produce positively charged amino groups.As a result,the cationic nanodisks possessed stronger tumor infiltration ability through transcytosis than anionic nanodisks.HCPT and TRAIL exerted synergistic antitumor effects with better overall therapeutic efficacy.This TRAIL-[ND-HCPT]^(GAC)system performed significantly better than free HCPT and remarkably prolonged the survival of breast tumor-bearing mice with no significant toxicity.

关 键 词:tumor penetration combination therapy charge reversal γ-glutamyl transpeptidase nanodisk 

分 类 号:R737.9[医药卫生—肿瘤]

 

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