{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:35:18Z","timestamp":1792024518784,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Despite advances in combination therapies for cancer treatment, most strategies rely on modular\u2010additive designs that lack dynamic molecular cues to achieve intrinsic synergy. Herein, a mitochondrial\u2010targeted nanoplatform is introduced that orchestrates photodynamic therapy (PDT), mild photothermal therapy (mPTT), and enzyme dynamic therapy (EDT) into a self\u2010amplifying cascade network through gasotransmitter (H\n                    <jats:sub>2<\/jats:sub>\n                    S)\u2010driven metabolic reprogramming. It is constructed from an Au\n                    <jats:sub>2<\/jats:sub>\n                    Pt core with a surface functionalized mesoporous silica shell loaded with photosensitizers, encapsulated within a tumor cell membrane (Au\n                    <jats:sub>2<\/jats:sub>\n                    Pt@4sMSN\/PS\u2010TPP@CM). Upon GSH exposure, nanomotors produce H\n                    <jats:sub>2<\/jats:sub>\n                    S to boost diffusive motion, while TPP targeting directs this motility toward mitochondria, enabling efficient mitochondrial accumulation (internalization of &gt;100\u00a0nm nanoparticles). Subsequently, mitochondrial targeted H\n                    <jats:sub>2<\/jats:sub>\n                    S releasing\u2010mediated suppression of oxidative phosphorylation amplifies PDT efficacy; HSP70 downregulation enables mPTT; and hyperactive glycolytic metabolism fuels EDT. Furthermore, these enhanced modalities also interconnect in a positive feedback loop: mPTT\u2010derived hyperthermia accelerates EDT\u2010catalyzed oxygen generation for PDT, while mitochondria\u2010localized PDT further inhibits HSP70 to boost mPTT. Ultimately, these interconnected molecular cues establish an H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010driven, self\u2010reinforcing therapeutic loop that enables effective eradication of hepatocellular carcinoma. Collectively, this study identifies mitochondria as the biological initiator and signal integrator for multimodal therapy, delivering a distinctive paradigm to overcome the limitations of conventional combination therapies.\n                  <\/jats:p>","DOI":"10.1002\/adma.202513757","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T07:20:51Z","timestamp":1764660051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mitochondria\u2010Targeted Nanomotor: H\n                    <sub>2<\/sub>\n                    S\u2010Driven Cascade Therapy for Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9900-8804","authenticated-orcid":false,"given":"Chengcheng","family":"Li","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Imaging and Interventional Medicine Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology Department of Radiology Lishui Central Hospital The Fifth Affiliated Hospital of Wenzhou Medical University  Lishui 323000 China"},{"name":"Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering \u00c5bo Akademi University Turku 20500 Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Ma","sequence":"additional","affiliation":[{"name":"Joint Centre of Translational Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine the First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000 China"},{"name":"Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering \u00c5bo Akademi University Turku 20500 Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiji","family":"Fang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Imaging and Interventional Medicine Zhejiang Engineering Research 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