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However, this mechanism contributes far less than the latter to Dox therapy. This newly identified pathway to make Dox therapy function like the combination of chemodynamic therapy (CDT) and chemotherapy\u2010mediated by Dox alone would be amplified. One\u2010pot nanoconstruction (HEBD) is fabricated based on the chemical reactions driven assemblies among epigallocatechin gallate (EGCG), buthionine sulfoximine (BSO) and formaldehyde in aqueous mediums followed by Dox adsorption. Acid tumor microenvironments allow the liberation of EGCG, BSO, and Dox due to the breakage of Schiff base bonds. EGCG component in HEBD is responsible for targeting mitochondria and disrupting mitochondrial electron transport chain (mETC) to compel electrons leakage in favor of their capture by Dox to produce more ROS. EGCG\u2010induced mETC disruption results in mitochondrial respiration inhibition with alleviated hypoxia in tumor cells while BSO inhibits glutathione biosynthesis to protect ROS from redox depletion, further boosting Dox\u2010induced CDT. This strategy of amplifying CDT pathway for the Dox\u2010mediated combined therapy could largely improve antitumor effect, extend lifespan of tumor\u2010bearing mice, reduce risks of cardiotoxicity and metastasis.<\/jats:p>","DOI":"10.1002\/adhm.202202045","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T05:04:10Z","timestamp":1665723850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Boosting Doxorubicin\u2010Induced Mitochondria Apoptosis for the Monodrug\u2010Mediated Combination of Chemotherapy and Chemodynamic Therapy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-2051","authenticated-orcid":false,"given":"Tao","family":"Liu","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 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