{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:02:41Z","timestamp":1789473761835,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Obesity\u2010driven lipid accumulation in hepatocellular carcinoma (HCC) establishes a coupled metabolic\u2010immunosuppressive niche that fuels tumor progression and undermines anti\u2010tumor immunity. Through multiplexed immunofluorescence profiling of clinical HCC tissues stratified by visceral adiposity, we explicitly map this lipid\u2010immunosuppressive landscape and demonstrate that fatty acid translocase CD36 overexpression directly correlates with FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      Treg infiltration and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell exclusion, defining a clinically actionable immunometabolic vulnerability. To therapeutically exploit this vulnerability, we engineer an AI\u2010designed, structure\u2010guided CD36\u2010occluding nanoplatform (LAIBP) with intrinsic ultrasound\u2010responsive sonodynamic capability. Mechanistically, LAIBP selectively blockades CD36\u2010mediated exogenous lipid influx to impose metabolic vulnerability; subsequent ultrasound activation triggers a spatiotemporally controlled oxidative burst, driving disulfidoptosis\u2010like cell death through NADPH depletion, redox imbalance, and cytoskeletal collapse in the lipid\u2010replete tumor microenvironment. Transcriptomic analysis and protein\u2010level validation indicate coordinated metabolic, redox, and immune\u2010associated changes, with G protein\u2010coupled receptor (GPCR)\u2010associated phosphatidylinositol 3\u2010kinase (PI3K)\/ serine\/threonine\u2010protein kinase (Akt)\/ Serine\/threonine\u2010protein kinase mTOR signaling and the cystine\/glutamate transporter (SLC7A11) \u2010 phospholipid hydroperoxide glutathione peroxidase(GPX4) axis emerging as pathways associated with the observed metabolic\u2010redox response. In obesity\u2010associated implanted HCC mouse models, LAIBP combined with ultrasound irradiation suppresses tumor growth, reduces intratumoral lipid accumulation, and is associated with remodeling of the tumor immune microenvironment. Collectively, this work supports a clinically grounded rationale and a nanotherapeutic framework for further immunometabolic investigation in obesity\u2010associated HCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The LAIBP nanoplatform, via the integrated paradigm of \u201cmetabolic entry blockade + redox homeostasis disruption + exogenous trigger amplification\u201d, induces metabolic collapse and disulfidoptosis\u2010like damage in HCC cells and is associated with remodeling of the antitumor immune microenvironment. This work supports a candidate sonodynamic, immunometabolism\u2010associated strategy for obesity\u2010associated HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/smll.75339","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:03:50Z","timestamp":1789470230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD36\u2010Pocket Targeting Induces Metabolic Collapse and Disulfidoptosis for Sonodynamic Immunometabolic Therapy of Liver Cancer"],"prefix":"10.1002","author":[{"given":"Liang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Xuzhou Central Hospital Southeast University  Xuzhou Jiangsu P. R. 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