{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:22:19Z","timestamp":1791285739194,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2022NSCQ\u2010MSX0120"],"award-info":[{"award-number":["CSTB2022NSCQ\u2010MSX0120"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Reactive oxygen species (ROS)\u2010mediated tumor therapy, which induces oxidative stress damage for precise oncolysis, represents a novel antitumor strategy. However, the overexpression of glutathione (GSH) in the tumor microenvironment (TME) forms a strong antioxidant barrier, rapidly scavenging ROS and repairing oxidative damage, thus limiting the efficacy of conventional ROS\u2010based therapies. Metal nanosonosensitizers, activated by ultrasound and penetrating deeply into the TME, offer a promising solution when combined with glutaminase1 (GLS1) inhibitors to overcome GSH\u2010mediated defenses. This study innovatively constructs a biomimetic metal nanosonosensitizer, CRIM, with a copper sulfide as core, encapsulating IR780 and IPN60090, coated with tumor cell membranes. CRIM specifically accumulates in tumor cell mitochondria, where ultrasound activation triggers efficient ROS generation while depleting GSH levels by direct consumption and indirect synthesis. This synergistic GSH depletion disrupts the tumor antioxidant system, sustaining ROS accumulation and triggering a ROS storm. The \u201cROS generation\u2010GSH depletion\u2010exacerbated oxidative stress\u201d feedback loop induces immunogenic cell death (ICD). Additionally, copper ion released from CRIM induces cuproptosis, synergizing with ROS\u2010mediated cytotoxicity to enhance therapeutic efficacy. This approach triggers a ROS storm via multi\u2010pathway synergy, induces comprehensive tumor destruction, and activates systemic immunity, thereby unleashing a potent antitumor force and offering a new direction for cancer treatment.<\/jats:p>","DOI":"10.1002\/smll.202513649","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:32:21Z","timestamp":1767871941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Unleashing the Potent Antitumor Force: A Reactive Oxygen Species (ROS) Storm Formation by Ultrasound\u2014Activatable Metal Nanosonosensitizers"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4098-7025","authenticated-orcid":false,"given":"Qi","family":"Xiang","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Ultrasound Molecular Imaging and Therapy, Ultrasound Department of the Second Affiliated Hospital 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