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Reactive oxygen species (ROS) have been widely applied in tumor therapy; however, the prevalent hypoxic conditions within tumors severely hinder the generation of ROS, leading to suboptimal antitumor efficacy. Herein, we designed an endogenous H2O2-triggered chlorine radical nanogenerator (Cl\u2022) and hydroxyl radicals(\u2022OH), which have better kinetic advantages and higher catalytic activity in catalyzing the H2O2 reaction. In vitro cytotoxicity tests revealed that the nano-urchins induced marked cancer cell death (up to \u223c80% at the highest tested concentration) in a concentration-dependent manner, attributable to the chlorine radical-mediated oxidative stress. Moreover, the H2O2-specific activation strategy reduces toxic side effects on normal tissues, thereby enhancing the safety of tumor therapy. Finally, compared with conventional Cu2O nanocatalysts that solely generate \u2022OH, our designed nano-urchins exhibit enhanced therapeutic efficacy, which is mainly attributed to the synergistic therapeutic effect. Therefore, our nano-urchins can serve as a novel nanocatalyst for tumor therapy.<\/jats:p>","DOI":"10.1021\/acsami.6c12768","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:10:31Z","timestamp":1785849031000},"page":"42428-42438","source":"Crossref","is-referenced-by-count":0,"title":["H2O2-Responsive Nanocatalysts for Synergistic Hydroxyl and Chlorine Radical-Mediated Tumor Therapy"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0546-6280","authenticated-orcid":true,"given":"Zhiming","family":"Deng","sequence":"first","affiliation":[{"name":"Hunan Institute of Science and Technology , , ,","place":["Yueyang, People\u2019s Republic of China, 414006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Hunan Institute of Science and Technology , , ,","place":["Yueyang, People\u2019s Republic of China, 414006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8095-6244","authenticated-orcid":true,"given":"Xingwang","family":"Wen","sequence":"additional","affiliation":[{"name":"Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences , , ,","place":["Ningbo, China, 315300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5353-4418","authenticated-orcid":true,"given":"Zizhong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]},{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JingJin","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Institute of Science and Technology , , ,","place":["Yueyang, People\u2019s Republic of China, 414006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoli","family":"Yin","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026081706065830200_cit1","doi-asserted-by":"publisher","first-page":"3427","DOI":"10.1038\/s41467-020-17242-0","article-title":"LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis","volume":"11","author":"Arra","year":"2020","journal-title":"Nat. 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