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Herein, we designed a polyporous Cu single atom nanozyme (Cu SAzyme) loaded with licogliflozin (LIK066) for HSP\u2010silencing induced mild PTT. On one hand, LIK066 inhibits glucose uptake by shutting sodium\u2010dependent glucose transporter (SGLT) \u201cvalve\u201d, effectively blocking the energy source for adenosine triphosphate (ATP) generation. Without sufficient energy, cancer cells cannot synthesize HSPs. On the other hand, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two\u2010pronged strategy of SGLT inhibitor and ROS storm, LIK066\u2010loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT.<\/jats:p>","DOI":"10.1002\/anie.202209245","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T17:15:01Z","timestamp":1666286101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":182,"title":["Cu Single Atom Nanozyme Based High\u2010Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation"],"prefix":"10.1002","volume":"61","author":[{"given":"Mengyu","family":"Chang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 P. R. 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