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In vitro and in vivo experiments using PDA\/Cu\/ICG\/R irradiated with an NIR laser demonstrate that when NIR is \u201cOFF,\u201d Cu<jats:sup>2+<\/jats:sup> can undergo Fenton\u2010like reaction in tumor cells, producing a large amount of hydroxyl radicals (\u00b7OH), which leads to oxidative stress in cells. This oxidative stress can cause mitochondrial oxidative phosphorylation dysfunction, resulting in limited ATP synthesis. When NIR is \u201cON,\u201d mild\u2010PTT can accelerate Cu<jats:sup>2+<\/jats:sup> to produce \u00b7OH. Simultaneously, NIR can activate ICG to produce reactive oxygen species (ROS) storm, amplify intracellular oxidative stress, and continuously damage mitochondria. The biodegradability of PDA greatly reduces the risk of toxicity caused by long\u2010term retention of PDA\/Cu\/ICG\/R in organisms. Finally, the improvement of the mild\u2010PTT effect of PDA is successfully achieved through the double mitochondrial destruction pathway of Cu<jats:sup>2+<\/jats:sup> and ICG controlled by NIR \u201cswitch.\u201d<\/jats:p>","DOI":"10.1002\/adhm.202300929","type":"journal-article","created":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T02:44:03Z","timestamp":1686365043000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A Dual Heat Shock Protein Down\u2010Regulation Strategy Using PDA\/Cu\/ICG\/R Controlled by NIR \u201cSwitch\u201d Enhances Mild\u2010Photothermal Therapy Effect"],"prefix":"10.1002","volume":"12","author":[{"given":"Xin","family":"Ding","sequence":"first","affiliation":[{"name":"Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province &amp; Institute of Advanced Materials and Nanotechnology College of Chemistry and Chemical Engineering Wuhan University of Science and Technology  Wuhan 430081 P. 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