{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:12:47Z","timestamp":1788970367919,"version":"build-2803163510"},"reference-count":47,"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\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"crossref","award":["22475166"],"award-info":[{"award-number":["22475166"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"crossref","award":["U24A20523"],"award-info":[{"award-number":["U24A20523"]}],"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>Photosensitizers in nanocrystals have emerged as promising avenues for immune stimulation through enhanced reactive oxygen species (ROS) generation relative to their amorphous structures. However, their rigid molecular packing severely restricts the molecular variations necessary for stimuli-responsive conversion in the crystalline state, resulting in challenges for these nanocrystals to undergo dynamic and on-demand immune regulation, particularly under the tumor microenvironment (TME) stimulation. Herein, we address this challenge by developing 2TZP, a photosensitizer engineered with a synergistic proton-capturing motif that confers a narrow pH response range within the TME. This design enables a specific and complete acid-triggered nanocrystal-to-nanocrystal (NCNC) transformation, from hexagonal prism to cuboid prism, directly activated by TME (pH 6.5) with a narrow response range of 0.70 pH units. This process involves significant conformational distortion, subtle rotation, and slippage within the preserved crystalline lattice, which is favored by sensitive responsiveness, sufficient free volume, and crystal lattice similarity before and after nanocrystal transformation. Crucially, this mechanism serves a dual purpose. It intensifies the twisted intramolecular charge transfer (TICT) effect, boosting intersystem crossing (ISC), while simultaneously unveiling latent RNA binding to form an electron reservoir pump and thereby enhancing ROS generation. Thus, the transformed 2TZP nanocrystals further potentiate their ability to target the nucleolus, causing oxidative damage to the nucleolus and leading to pronounced nuclear disruption and enhanced dsDNA leakage. This then effectively ensures potent, on-demand activation of the cGAS-STING immune pathway while concurrently inducing robust immunogenic cell death (ICD) under an acidic TME. This work not only demonstrates a model of NCNC transformation within the TME, but also establishes a design principle to couple structural regulation with dynamic, on-demand function amplification for potential photoimmunotherapy.<\/jats:p>","DOI":"10.1021\/jacs.6c03436","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:24Z","timestamp":1788263424000},"page":"37696-37714","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Microenvironment-Triggered\nNanocrystal-to-Nanocrystal\nTransformation for RNA-Boosted Photo-STING Therapy"],"prefix":"10.1021","volume":"148","author":[{"given":"Peijuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Harbin Engineering University , , ,","place":["Qingdao, P. R. China, 266000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]},{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifei","family":"Shen","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianshao","family":"Zou","sequence":"additional","affiliation":[{"name":"Harbin Engineering University , , ,","place":["Qingdao, P. R. China, 266000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-9780","authenticated-orcid":true,"given":"Lingjie","family":"Meng","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]},{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-9632","authenticated-orcid":true,"given":"Dongfeng","family":"Dang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiao Tong University , , ,","place":["Xi\u2019an, P. R. China, 710049"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026090910090118300_cit1","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the\ntumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat. Med."},{"key":"2026090910090118300_cit2","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1038\/s41568-024-00699-2","article-title":"Exploiting\ntemporal aspects of cancer immunotherapy","volume":"24","author":"Zemek","year":"2024","journal-title":"Nat.\nRev. Cancer"},{"key":"2026090910090118300_cit3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202417899","article-title":"Photon-driven dye induction pyroptosis:\nAn emerging anti-tumor immunotherapy\nparadigm","volume":"64","author":"Zeng","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090910090118300_cit4","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41586-023-06889-6","article-title":"MRE11 liberates cGAS from nucleosome sequestration\nduring tumorigenesis","volume":"625","author":"Cho","year":"2024","journal-title":"Nature"},{"key":"2026090910090118300_cit5","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/s43018-022-00468-w","article-title":"The cGAS-STING pathway and cancer","volume":"3","author":"Samson","year":"2022","journal-title":"Nat. Cancer"},{"key":"2026090910090118300_cit6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.immuni.2025.11.004","article-title":"A chemical agonist\nand the Golgi-resident lipid PI4P activate STING by inducing transmembrane\nhelix rearrangement","volume":"59","author":"Han","year":"2026","journal-title":"Immunity"},{"key":"2026090910090118300_cit7","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41568-025-00894-9","article-title":"Opportunities\nand challenges of targeting\ncGAS-STING in cancer","volume":"26","author":"Lu","year":"2026","journal-title":"Nat. Rev. Cancer"},{"key":"2026090910090118300_cit8","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202509416","article-title":"Rational\ndesign of type-I photodynamic agents","volume":"64","author":"Teng","year":"2025","journal-title":"Angew.\nChem., Int. 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Ed."},{"key":"2026090910090118300_cit12","doi-asserted-by":"publisher","first-page":"4871","DOI":"10.1021\/jacs.4c13241","article-title":"A second near-infrared\nwindow-responsive metal-organic-framework-based photosensitizer for\ntumor immunotherapy via synergistic ferroptosis and\nSTING activation","volume":"147","author":"Zhao","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit13","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202405358","article-title":"Eosinophil-activating\nsemiconducting polymer nanoparticles\nfor cancer photo-immunotherapy","volume":"63","author":"Zhang","year":"2024","journal-title":"Angew. Chem.,\nInt. Ed."},{"key":"2026090910090118300_cit14","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202305668","article-title":"Bioorthogonal guided\nactivation of cGAS-STING by AIE photosensitizer\nnanoparticles for targeted tumor therapy and imaging","volume":"35","author":"Cui","year":"2023","journal-title":"Adv. Mater."},{"key":"2026090910090118300_cit15","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201803325","article-title":"Simultaneous increase in brightness and singlet oxygen generation\nof an organic photosensitizer by nanocrystallization","volume":"14","author":"Fateminia","year":"2018","journal-title":"Small"},{"key":"2026090910090118300_cit16","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202402434","article-title":"Less is More:\nAsymmetric D\u2013A\nType Agent to Achieve Dynamic Self-Assembled Nanoaggregates for Long-Acting\nPhotodynamic Therapy","volume":"36","author":"Xu","year":"2024","journal-title":"Adv. Mater."},{"key":"2026090910090118300_cit17","doi-asserted-by":"publisher","first-page":"41973","DOI":"10.1021\/jacs.5c15153","article-title":"Cationic nano single crystals: from in situ structural\ndetermination to synergistic photoimmunotherapy","volume":"147","author":"Zhang","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit18","doi-asserted-by":"publisher","first-page":"17772","DOI":"10.1021\/jacs.5c01145","article-title":"Regulating reversible\nuntwisting and twisting motions in helical dynamic molecular crystals","volume":"147","author":"Qiu","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit19","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.1021\/jacs.0c12153","article-title":"Emission-tunable\nsoft porous organic crystal based on squaraine for single-crystal\nanalysis of guest-induced gate-opening transformation","volume":"143","author":"Li","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit20","doi-asserted-by":"publisher","first-page":"4210","DOI":"10.1021\/jacs.4c14130","article-title":"Superhydrophobic and self-healing porous organic macrocycle\ncrystals for methane purification under humid conditions","volume":"147","author":"Wang","year":"2025","journal-title":"J. Am. Chem. 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Soc."},{"key":"2026090910090118300_cit24","doi-asserted-by":"publisher","first-page":"29237","DOI":"10.1021\/jacs.4c12532","article-title":"Photoswitchable\nazobispyrazole crystals achieving near-quantitative crystalline-state\nbidirectional E\u21c4Z conversions","volume":"146","author":"He","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit25","doi-asserted-by":"publisher","first-page":"25998","DOI":"10.1021\/jacs.5c08796","article-title":"Unveiling migration\ndynamics of acid molecules in microenvironments via fluorescence signal: A case study in polymer emulsion film formation","volume":"147","author":"Wang","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit26","doi-asserted-by":"publisher","first-page":"18350","DOI":"10.1021\/jacs.4c02954","article-title":"Mechanochemical\nfabrication of full-color luminescent materials from aggregation-induced\nemission prefluorophores for information storage and encryption","volume":"146","author":"Xie","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit27","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s00894-021-04884-0","article-title":"Simple, reliable,\nand universal metrics of molecular planarity","volume":"27","author":"Lu","year":"2021","journal-title":"J. Mol. Model."},{"key":"2026090910090118300_cit28","doi-asserted-by":"publisher","first-page":"5359","DOI":"10.1021\/jacs.8b13889","article-title":"Molecular\nmotion in aggregates: Manipulating TICT for boosting photothermal\ntheranostics","volume":"141","author":"Liu","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit29","doi-asserted-by":"publisher","first-page":"10160","DOI":"10.1002\/anie.201916357","article-title":"Quantitative design\nof bright fluorophores and AIEgens by the accurate prediction of twisted\nintramolecular charge transfer (TICT)","volume":"59","author":"Wang","year":"2020","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026090910090118300_cit30","doi-asserted-by":"publisher","first-page":"2311404","DOI":"10.1002\/adfm.202311404","article-title":"Integrating\naggregation induced emission\nand twisted intramolecular charge transfer via molecular\nengineering","volume":"34","author":"Zhang","year":"2024","journal-title":"Adv. Funct. Mater."},{"key":"2026090910090118300_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202516764","article-title":"Phase-transition nanoparticles enable fluorescence self-reporting\nfor close-loop photodynamic therapy","volume":"64","author":"Zhang","year":"2025","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026090910090118300_cit32","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1021\/jacs.1c11231","article-title":"Energy counterbalance\nto harness photoinduced structural planarization of dibenzo[b,f]azepines toward thermal reversibility","volume":"144","author":"Chen","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit33","doi-asserted-by":"publisher","first-page":"12656","DOI":"10.1039\/D1CS00239B","article-title":"Twisted intramolecular\ncharge transfer (TICT) and twists beyond TICT: from mechanisms to\nrational designs of bright and sensitive fluorophores","volume":"50","author":"Wang","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"2026090910090118300_cit34","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202506412","article-title":"A hypoxia-triggered\nbioreduction of hydrophilic type I photosensitizer\nfor switchable in vivo photoacoustic imaging and\nhigh-specificity cancer phototherapy","volume":"64","author":"Zhao","year":"2025","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026090910090118300_cit35","doi-asserted-by":"publisher","first-page":"5589","DOI":"10.1039\/C6CS00176A","article-title":"Peptide self-assembly: Thermodynamics\nand kinetics","volume":"45","author":"Wang","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"2026090910090118300_cit36","doi-asserted-by":"publisher","first-page":"22176","DOI":"10.1021\/jacs.3c08257","article-title":"From helices\nto crystals: Multiscale representation\nof chirality in double-helix structures","volume":"145","author":"Li","year":"2023","journal-title":"J.\nAm. Chem. Soc."},{"key":"2026090910090118300_cit37","doi-asserted-by":"publisher","first-page":"25270","DOI":"10.1021\/jacs.4c09470","article-title":"RNA-activatable\nnear-infrared photosensitizer\nfor cancer therapy","volume":"146","author":"Jiang","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit38","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202309743","article-title":"RNA buffering fluorogenic\nprobe for\nnucleolar morphology stable imaging and nucleolar stress-generating\nagents screening","volume":"11","author":"Jiang","year":"2024","journal-title":"Adv. Sci."},{"key":"2026090910090118300_cit39","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.cell.2025.01.005","article-title":"Cellular responses\nto RNA damage","volume":"188","author":"Cordes","year":"2025","journal-title":"Cell"},{"key":"2026090910090118300_cit40","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1038\/s44222-025-00342-1","article-title":"In vivo, clinical\nand translational aspects of aggregation-induced emission","volume":"3","author":"Yan","year":"2025","journal-title":"Nat. Rev. Bioeng."},{"key":"2026090910090118300_cit41","doi-asserted-by":"publisher","first-page":"7433","DOI":"10.1021\/jacs.4c15534","article-title":"Pyridinium rotor strategy toward\na robust photothermal agent for STING activation and multimodal image-guided\nimmunotherapy for Triple-Negative Breast Cancer","volume":"147","author":"Ning","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit42","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41581-024-00819-z","article-title":"Physiological\nprinciples\nunderlying the kidney targeting of renal nanomedicines","volume":"20","author":"Huang","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"2026090910090118300_cit43","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1681\/ASN.0000000608","article-title":"Nanotherapeutics in\nkidney disease: Innovations, challenges, and future Directions","volume":"36","author":"Roointan","year":"2025","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026090910090118300_cit44","doi-asserted-by":"publisher","first-page":"10395","DOI":"10.1038\/s41467-024-53906-x","article-title":"A hypoxia-activated\nand microenvironment-remodeling nanoplatform for multifunctional imaging\nand potentiated immunotherapy of cancer","volume":"15","author":"Song","year":"2024","journal-title":"Nat.\nCommun."},{"key":"2026090910090118300_cit45","doi-asserted-by":"publisher","first-page":"34669","DOI":"10.1021\/jacs.4c13022","article-title":"Sonodynamic nano-LYTACs\nreverse tumor immunosuppressive microenvironment for cancer immunotherapy","volume":"146","author":"Xu","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910090118300_cit46","doi-asserted-by":"publisher","first-page":"9417","DOI":"10.1038\/s41467-024-53771-8","article-title":"Self-assembled aldehyde dehydrogenase-activatable nano-prodrug\nfor cancer stem cell-enriched tumor detection and treatment","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"2026090910090118300_cit47","doi-asserted-by":"publisher","first-page":"28973","DOI":"10.1021\/jacs.4c09831","article-title":"A type I photosensitizer-polymersome\nboosts reactive oxygen species generation by forcing H-aggregation\nfor amplifying STING immunotherapy","volume":"146","author":"Wang","year":"2024","journal-title":"J. Am. Chem.\nSoc."}],"container-title":["Journal of the American\nChemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c03436","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/35\/37696\/67427095\/jacs.6c03436.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/35\/37696\/67427095\/jacs.6c03436.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:28:15Z","timestamp":1788967695000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/35\/37696\/5330489\/Tumor-Microenvironment-Triggered-Nanocrystal-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":47,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2026,8,26]]},"published-print":{"date-parts":[[2026,9,9]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c03436","relation":{},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}