Precisely albumin-hitchhiking tumor cell-activated reduction/oxidation-responsive docetaxel prodrugs for the hyperselective treatment of breast cancer

Journal of Controlled Release : Official Journal of the Controlled Release Society
Wei WeiZhonggui He

Abstract

The anticancer efficacy of chemotherapy is greatly limited by short blood circulation and poor tumor selectivity. Thus, anticancer prodrugs with prolonged systemic circulation, tumor-specific distribution and bioactivation, could significantly strengthen the chemotherapy efficacy. Herein, we design two novel tumor cell reduction/oxidation-responsive docetaxel (DTX) prodrugs, DTX-maleimide conjugates with disulfide bond (DSSM) or thioether bond (DSM) linkages, to evaluate the roles of different sensitive linkages in drug release, pharmacokinetics and therapeutic efficacy. An ester bond-linkage prodrug (DM) is utilized as a non-sensitive control. DSSM and DSM show reduction- or oxidation-sensitive release behavior, respectively, and exhibit hyperselective bioactivation and cytotoxicities between cancerous and normal cells. They could instantly hitchhike blood circulating albumin after i.v. administration with albumin-binding half-lives as short as 1 min, resulting in prolonged systemic circulation, increased tumor accumulation. In response to the upregulated reduction/oxidation environment within tumor cells, DSSM and DSM exhibit selectively release capacity in tumor tissues, their TAITumor/Liver values are over 30-fold greater t...Continue Reading

Citations

Dec 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fatemeh ArasteMona Alibolandi
Aug 18, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Xinquan LiuDebadyuti Ghosh
Apr 10, 2021·Biomaterials·Yachao ZhangShuangying Gui
Jul 30, 2021·Advanced Science·Yuezhou ZhangWei Huang

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