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In this study, we identified extracellular magnesium (Mg2+) as a pharmacologically modulable regulator of CAR T activity. Mg2+ supplementation increased early activation and augmented cytotoxic readouts, including IFN-\u03b3 secretion and target-cell lysis. To localize this cue, we engineered a phosphorylated hyaluronic-acid hydrogel ionically cross-linked by Mg2+ (HA-Mg Gel), which forms an in situ Mg2+-rich niche. In this niche, CAR T cells exhibit reinforced actin polymerization at the tumor-T-cell interface and show enhanced activation and effector function in vitro. In a Capan-2 peritoneal metastasis model, intraperitoneal administration of CAR T@HA-Mg Gel produced durable tumor control and significantly prolonged survival compared with controls. These findings position extracellular Mg2+ as a modulator of CAR T activity and present a biomaterial-guided, nongenetic strategy to improve CAR T-cell therapy for solid tumors.<\/jats:p>","DOI":"10.1021\/acsami.6c06142","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:48:33Z","timestamp":1788454113000},"page":"48695-48703","source":"Crossref","is-referenced-by-count":0,"title":["Delivery of CAR T Cells in a Magnesium-Functionated Hydrogel Boosts Peritoneal Metastasis Treatment"],"prefix":"10.1021","volume":"18","author":[{"given":"Junlin","family":"Li","sequence":"first","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xutao","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Ren","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Liao","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huipeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Shi","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gong","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Lv","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-4456","authenticated-orcid":true,"given":"Zhen","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310016"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310027"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-8445","authenticated-orcid":true,"given":"Hongjun","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"9","key":"2026092321453168600_cit1","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/s44222-024-00198-x","article-title":"Engineering Cells for Therapy and Diagnosis","volume":"2","author":"Li","year":"2024","journal-title":"Nat. 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