{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:12:07Z","timestamp":1788970327939,"version":"build-2803163510"},"reference-count":68,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFA1203902"],"award-info":[{"award-number":["2022YFA1203902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Natural Science Foundation-Haidian Primitive Innovation Joint Fund","award":["L232015"],"award-info":[{"award-number":["L232015"]}]},{"name":"Fundamental Research Funds for the Central Universities, Peking University","award":["PKU2024LCXQ014 and PKU2025PKULCXQ040"],"award-info":[{"award-number":["PKU2024LCXQ014 and PKU2025PKULCXQ040"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"crossref","award":["92263203, 52027801, 22575006, 52201198"],"award-info":[{"award-number":["92263203, 52027801, 22575006, 52201198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Integrating localized amino acid perturbation with systemic metabolic regulation represents a compelling strategy to exploit tumor metabolic vulnerabilities. However, current metabolic modulators remain challenged by poor tumor selectivity, limited oral bioavailability, and reliance on complex delivery systems that hinder clinical translation. Here, we report a fasting-augmented amino acid intervention strategy using iron\u2013cystine spherulites (FeCST). Following oral administration, FeCST is converted in the stomach into ultrasmall cystine nanoparticles (FeCST-NPs) that traverse intestinal mucus and enter systemic circulation via the paracellular pathway. In the bloodstream, FeCST-NPs spontaneously reassemble with specific plasma proteins into nanoclusters, which may contribute to their preferential accumulation in tumors. Synergistically, FeCST and intermittent fasting (IF) robustly induce disulfidptosis, resulting in potent tumor suppression and enhanced antitumor immunity. This synergistic effect is associated with multiple IF-induced metabolic alterations, including glucose restriction and transient modulation of intestinal epithelial permeability, which collectively facilitate FeCST bioavailability and increase tumor susceptibility to disulfide stress. This study presents a disulfidptosis-mediated paradigm that integrates controlled amino acid intervention with fasting-mediated systemic metabolic modulation.<\/jats:p>","DOI":"10.1021\/jacs.6c08989","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:21Z","timestamp":1788263421000},"page":"37954-37970","source":"Crossref","is-referenced-by-count":0,"title":["Blood-Triggered\nIn Vivo Reassembly of Oral Cystine\nSpherulites with Fasting Synergy Induces Disulfidptosis for Cancer\nMetabolic Intervention"],"prefix":"10.1021","volume":"148","author":[{"given":"Ran","family":"Ma","sequence":"first","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1647-0643","authenticated-orcid":true,"given":"Shuren","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]},{"name":"Shenzhen Campus of Sun Yat-Sen University , , ,","place":["Shenzhen, China, 518107"]},{"name":"State Key Laboratory of Optoelectronic Materials and Technologies , ,","place":["Guangzhou, China, 510275"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Liu","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhe","family":"Ma","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, China, 200438"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Beijing Technology and Business University , , ,","place":["Beijing, China, 100048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Peng","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0579-4594","authenticated-orcid":true,"given":"Yanglong","family":"Hou","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]},{"name":"Shenzhen Campus of Sun Yat-Sen University , , ,","place":["Shenzhen, China, 518107"]},{"name":"State Key Laboratory of Optoelectronic Materials and Technologies , ,","place":["Guangzhou, China, 510275"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026090910093307300_cit1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer\nprogression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"2026090910093307300_cit2","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41565-024-01733-y","article-title":"An artificial\nmetabzyme for tumour-cell-specific metabolic therapy","volume":"19","author":"Hu","year":"2024","journal-title":"Nat. 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Cancer"},{"key":"2026090910093307300_cit5","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","article-title":"Understanding the Intersections between\nMetabolism and Cancer Biology","volume":"168","author":"Vander Heiden","year":"2017","journal-title":"Cell"},{"key":"2026090910093307300_cit6","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks\nof Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab"},{"key":"2026090910093307300_cit7","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/s41416-019-0620-5","article-title":"New aspects of amino acid metabolism\nin cancer","volume":"122","author":"Vettore","year":"2020","journal-title":"Br. J. 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