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Nonetheless, their clinical application has been impeded by two primary limitations: the inadequate generation of reactive oxygen species (ROS) upon X-ray irradiation and insufficient penetration into the tumor tissues. Herein, we developed an aggregation-induced emission nanoassembly (TTVP NPs) specifically engineered for enhanced radiotherapy in breast cancer. Benefiting from their ultrasmall particle size and positive surface charge, TTVP NPs showed a rapid tumor penetration and efficient cellular internalization. Comprehensive mechanistic investigations through immunofluorescence staining, Western blot analysis, and transcriptomic profiling revealed that TTVP NPs demonstrate an enhanced therapeutic efficacy under X-ray irradiation via (1) efficient conversion of radiation energy to cytotoxic ROS, (2) induction of DNA breaks, and (3) suppression of DNA damage repair, thereby significantly inhibiting cancer cell proliferation and activating apoptotic pathways. In orthotopic breast cancer models, the combination of TTVP NPs with X-ray irradiation suppressed tumor growth, supporting the radiosensitizing activity of the TTVP NPs. Notably, this efficacy was also observed in patient-derived organoids, where TTVP NPs successfully penetrated the tumor barrier and consistently induced significant DNA strand breaks across clinically derived samples with X-ray irradiation, validating their potential as promising radiosensitizer candidates in precision radiotherapy.<\/jats:p>","DOI":"10.1021\/acsnano.6c00356","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:01:58Z","timestamp":1790395318000},"page":"27002-27018","source":"Crossref","is-referenced-by-count":0,"title":["Aggregation-Induced\nEmission Nanoassembly with Enhanced\nRadiosensitization for Boosting Breast Cancer Radiotherapy"],"prefix":"10.1021","volume":"20","author":[{"given":"Ruonan","family":"Li","sequence":"first","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Tang","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannan","family":"Wu","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Luo","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Lin","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyu","family":"Han","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Kang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxun","family":"Ding","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7709-0508","authenticated-orcid":true,"given":"Yue","family":"Pan","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen University , , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5137-0771","authenticated-orcid":true,"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0293-964X","authenticated-orcid":true,"given":"Ben Zhong","family":"Tang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]},{"name":"The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen) , , ,","place":["Guangdong, China, 518172"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"3","key":"2026101310083507700_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN\nEstimates of Incidence and Mortality Worldwide for 36 Cancers in 185\nCountries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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Mater."},{"issue":"15","key":"2026101310083507700_cit18","doi-asserted-by":"publisher","first-page":"14972","DOI":"10.1021\/acsnano.5c00942","article-title":"Organic Radiosensitizer\nwith Aggregation-Induced Emission Characteristics\nfor Tumor Ablation through Synergistic Apoptosis and Immunogenic Cell\nDeath","volume":"19","author":"Xie","year":"2025","journal-title":"ACS Nano"},{"issue":"26","key":"2026101310083507700_cit19","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202302395","article-title":"Pure Organic AIE Nanoscintillator\nfor X-ray Mediated\nType I and Type II Photodynamic Therapy","volume":"10","author":"Yu","year":"2023","journal-title":"Adv.\nSci."},{"issue":"35","key":"2026101310083507700_cit20","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202502898","article-title":"Organic AIE Nanoradiosensitizer\nPotentiates X-Ray Triggered Continuous\nReactive Oxygen Species Generation for Potent Cancer Radioimmunotherapy","volume":"37","author":"Xu","year":"2025","journal-title":"Adv. Mater."},{"issue":"6","key":"2026101310083507700_cit21","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1039\/D1CS01138C","article-title":"The Fast-Growing Field of Photo-Driven Theranostics\nBased on Aggregation-Induced Emission","volume":"51","author":"Zhang","year":"2022","journal-title":"Chem.\nSoc. Rev."},{"issue":"45","key":"2026101310083507700_cit22","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201801350","article-title":"Photosensitizers with Aggregation-Induced Emission:\nMaterials and Biomedical Applications","volume":"30","author":"Hu","year":"2018","journal-title":"Adv.\nMater."},{"issue":"4","key":"2026101310083507700_cit23","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1039\/C9CS00495E","article-title":"Supramolecular Materials\nBased on AIE Luminogens (AIEgens):\nConstruction and Applications","volume":"49","author":"Li","year":"2020","journal-title":"Chem. Soc. Rev."},{"issue":"13","key":"2026101310083507700_cit24","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1039\/C4CS00044G","article-title":"AIE Macromolecules:\nSyntheses, Structures\nand Functionalities","volume":"43","author":"Hu","year":"2014","journal-title":"Chem. Soc. Rev."},{"issue":"5","key":"2026101310083507700_cit25","doi-asserted-by":"publisher","DOI":"10.1002\/agt2.575","article-title":"Elaborately Engineered\nAu(I)-Based AIEgens: Robust and Broad-Spectrum\nElimination Abilities Toward Drug-Resistant Bacteria","volume":"5","author":"Deng","year":"2024","journal-title":"Aggregate"},{"issue":"3","key":"2026101310083507700_cit26","doi-asserted-by":"publisher","DOI":"10.1002\/agt2.518","article-title":"Metal\u2013Organic\nFrameworks with Aggregation-Induced Emission","volume":"5","author":"Xu","year":"2024","journal-title":"Aggregate"},{"issue":"3","key":"2026101310083507700_cit27","doi-asserted-by":"publisher","DOI":"10.1002\/agt2.615","article-title":"Front Cover: Near-Infrared Aggregation-Induced\nEmission Materials:\nBibliometric Analysis and Their Application in Biomedical Field","volume":"5","author":"He","year":"2024","journal-title":"Aggregate"},{"key":"2026101310083507700_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.101084","article-title":"ROS and\nThe DNA Damage Response in Cancer","volume":"25","author":"Srinivas","year":"2019","journal-title":"Redox Biol."},{"issue":"8","key":"2026101310083507700_cit29","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413518","article-title":"Nitric Oxide-Releasing\nNanoscale Metal-Organic Layer Overcomes Hypoxia and Reactive Oxygen\nSpecies Diffusion Barriers to Enhance Cancer Radiotherapy","volume":"12","author":"Xiong","year":"2025","journal-title":"Adv. Sci."},{"issue":"3","key":"2026101310083507700_cit30","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial Reactive Oxygen Species\n(ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol.\nRev."},{"issue":"22","key":"2026101310083507700_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417370","article-title":"Camouflaged Nanozymes with Oxidation-Promoting\nActivities Triggering Ferroptosis for Radio-Immunotherapy","volume":"12","author":"Qiao","year":"2025","journal-title":"Adv. Sci."},{"issue":"12","key":"2026101310083507700_cit32","doi-asserted-by":"publisher","first-page":"11345","DOI":"10.1021\/acsnano.3c00350","article-title":"Glutathione-Exhausting\nNanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting\nRadiation Therapy Efficacy via Ferroptosis in Breast Cancer","volume":"17","author":"Wei","year":"2023","journal-title":"ACS Nano"},{"issue":"30","key":"2026101310083507700_cit33","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202504524","article-title":"Au(6)Cu(2)\nClusters with High Electron Affinity and Oxygen-Mimetic Properties\nfor Hypoxic Tumor Radiosensitization","volume":"64","author":"Zhao","year":"2025","journal-title":"Angew.\nChem., Int. Ed."},{"issue":"1","key":"2026101310083507700_cit34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52278-6","article-title":"Biodegradable\nCopper-Iodide Clusters Modulate Mitochondrial Function and Suppress\nTumor Growth Under Ultralow-Dose X-ray Irradiation","volume":"15","author":"Ma","year":"2024","journal-title":"Nat. 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Controlled Release"},{"issue":"15","key":"2026101310083507700_cit37","doi-asserted-by":"publisher","first-page":"3685","DOI":"10.1039\/C7SC04963C","article-title":"Rational\ndesign of a water-soluble NIR AIEgen, and its application in ultrafast\nwash-free cellular imaging and photodynamic cancer cell ablation","volume":"9","author":"Wang","year":"2018","journal-title":"Chem. Sci."},{"issue":"31","key":"2026101310083507700_cit38","doi-asserted-by":"publisher","first-page":"14388","DOI":"10.1021\/jacs.2c06111","article-title":"Nanolab in a cell: crystallization-induced\nin situ self-assembly for cancer theranostic amplification","volume":"144","author":"Wang","year":"2022","journal-title":"J. Am. Chem. Soc."},{"issue":"13","key":"2026101310083507700_cit39","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202419418","article-title":"A PD-L1 siRNA-Loaded Boron Nanoparticle for Targeted Cancer Radiotherapy\nand Immunotherapy","volume":"37","author":"Deng","year":"2025","journal-title":"Adv. Mater."},{"issue":"2","key":"2026101310083507700_cit40","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41571-021-00579-w","article-title":"Radiotherapy\nas A Tool to Elicit Clinically Actionable Signalling Pathways in Cancer","volume":"19","author":"Petroni","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"1\u20132","key":"2026101310083507700_cit41","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.cell.2017.11.010","article-title":"A Living Biobank\nof Breast Cancer Organoids Captures Disease Heterogeneity","volume":"172","author":"Sachs","year":"2018","journal-title":"Cell"},{"issue":"21","key":"2026101310083507700_cit42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI175824","article-title":"FDA Modernization\nAct 2.0: Transitioning\nBeyond Animal Models with Human Cells, Organoids, and AI\/ML-Based\nApproaches","volume":"133","author":"Zushin","year":"2023","journal-title":"J. Clin. Invest."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.6c00356","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/40\/27002\/68664760\/acsnano.6c00356.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/40\/27002\/68664760\/acsnano.6c00356.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:43:40Z","timestamp":1791917020000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/20\/40\/27002\/5439238\/Aggregation-Induced-Emission-Nanoassembly-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":42,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,9,25]]},"published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.6c00356","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]}}}