{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:12:23Z","timestamp":1792581143403,"version":"4.5.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52473140"],"award-info":[{"award-number":["52473140"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fujian Provincial Natural Science Foundation of China","award":["2026J008029"],"award-info":[{"award-number":["2026J008029"]}]},{"name":"Regional Innovation Cooperation Project of Sichuan Provincial Department of Science and Technology","award":["2026YFHZ0101"],"award-info":[{"award-number":["2026YFHZ0101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The clinical efficacy of cancer immunotherapy is fundamentally constrained by the synergistic evasion mechanisms of antigen concealment and effector immune cell suppression. To overcome these barriers, we proposed a therapeutic paradigm that sequentially dismantles the tumor\u2019s \u201cimmune camouflage\u201d and relieves \u201cmetabolic coercion,\u201d thereby enabling systematic remodeling of the tumor immune microenvironment. A cascade-acting nano-Proteolysis Targeting Chimera (PROTAC) engine was fabricated via phosphatidylcholine-driven self-assembly, enabling tumor-targeted delivery and pH-responsive drug release within the tumor microenvironment. The system initially disrupted the tumor\u2019s immune evasion barrier by inducing cellular senescence and enhancing MHC-I-mediated antigen presentation. It subsequently reprogrammed tumor metabolism through targeted degradation of the BRD4\/c-Myc axis, which alleviated nutrient competition and reversed the metabolic suppression of tumor-infiltrating T cells. This sequential intervention potently enhanced dendritic cell activation and antigen-presenting capacity, promoted the infiltration and reactivation of cytotoxic T lymphocytes, and synergistically induced PD-L1 degradation. Collectively, these coordinated effects established a durable antitumor immune response that potently suppressed both primary tumor growth and distant metastasis in a triple-negative breast cancer model. Overall, this work established a cascaded immune remodeling paradigm, conceptualized as unmasking and unblocking, offering a broadly applicable therapeutic strategy to overcome immunosuppression in solid tumors.<\/jats:p>","DOI":"10.1021\/acsnano.6c05863","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:16:07Z","timestamp":1785849367000},"page":"21884-21900","source":"Crossref","is-referenced-by-count":1,"title":["Sequential Disruption\nof Tumor Camouflage and Metabolic\nCoercion by Cascade-Acting Nano-Proteolysis Targeting Chimera Engines\nto Reprogram the Immune Ecosystem"],"prefix":"10.1021","volume":"20","author":[{"given":"Yazhen","family":"Wang","sequence":"first","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610064"]},{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610041"]},{"name":"Xiamen University , , ,","place":["Xiamen, China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Du","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxing","family":"Yan","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0939-9869","authenticated-orcid":true,"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwei","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, People\u2019s Republic of China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-7238","authenticated-orcid":true,"given":"Huile","family":"Gao","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-2299","authenticated-orcid":true,"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, P. R. 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