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However, within tumor, the relatively deficient concentration of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, hypoxic microenvironment, and overexpressed reduced glutathione (GSH)\u00a0seriously suppress the efficacy of dynamic therapy. Herein, a multi\u2010functional cascade nanoreactor, bovine serum albumin modified ZnO<jats:sub>2<\/jats:sub>@CeO<jats:sub>2<\/jats:sub>\u2010ICG, is reported for remodeling tumor microenvironment (TME) to boost dynamic therapy and realize mitochondria dysfunction via reactive oxygen species (ROS) storm\/Zn<jats:sup>2+<\/jats:sup> ions overload. Within TME, ZnO<jats:sub>2<\/jats:sub> decomposed into exogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and Zn<jats:sup>2+<\/jats:sup> ion. The dual enzyme\u2010like CeO<jats:sub>2<\/jats:sub> catalyzes the increased H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> into \u00b7OH and oxygen molecules respectively, and then the oxygen molecules are translated into <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub> by indocyanine green (ICG) under 808 nm light irradiation to boost PDT. The effective consumption of GSH through the reduction of Ce(IV) ions not only regenerates Ce(III) ions to enhance the efficiency of CDT but also efficaciously alleviates the elimination of ROS generated by dynamic therapy to further improve dynamic therapeutic efficiency. So the improved ROS level under remodeling TME and Zn<jats:sup>2+<\/jats:sup> ions acutely lead to mitochondria dysfunction to boost the efficiency of antitumor treatment. Thus, developing functional nanoreactors that enable remodeling TME provides a potential strategy to enhance the efficiency of dynamic therapy.<\/jats:p>","DOI":"10.1002\/smll.202408639","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T06:16:01Z","timestamp":1731564961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Multi\u2010Functional Cascade Nanoreactor for Remodeling Tumor Microenvironment to Realize Mitochondria Dysfunction via ROS\/Zn<sup>2+<\/sup> Ions Overload"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0248-5916","authenticated-orcid":false,"given":"Longhai","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Radiology The Second Hospital of Jilin University  Changchun 130041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry (CIAC) Chinese Academy of Sciences(CAS)  Changchun 130022 China"},{"name":"University of Science and Technology of China  Hefei Anhui 230026 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Hospital of Jilin University  Changchun 130041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Radiology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan 250014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijia","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Hospital of Jilin University  Changchun 130041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Hospital of Jilin University  Changchun 130041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Hospital of Jilin University  Changchun 130041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry (CIAC) Chinese Academy of Sciences(CAS)  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry (CIAC) Chinese Academy of Sciences(CAS)  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Guangzhou Medical University  Guangzhou 511436 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry (CIAC) Chinese Academy of Sciences(CAS)  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-8702","authenticated-orcid":false,"given":"Jianhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Hospital of Jilin University  Changchun 130041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.9b00448"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103836"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2020.100851"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12865"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.06.081"},{"key":"e_1_2_8_6_1","first-page":"20","volume":"10","author":"Ma G. 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