{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T10:31:21Z","timestamp":1793442681838,"version":"4.5.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2412035"],"award-info":[{"award-number":["W2412035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404537"],"award-info":[{"award-number":["82404537"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473859"],"award-info":[{"award-number":["82473859"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Province Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2023YQ065"],"award-info":[{"award-number":["ZR2023YQ065"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Controlled Release"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.jconrel.2026.115409","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:46:06Z","timestamp":1790264766000},"page":"115409","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"PB","title":["Radiotherapy-ignited dual-stage prodrug nanoplatform for cascade activation of toll-like receptor 7\/8 agonist and reignition of antitumor immunity"],"prefix":"10.1016","volume":"399","author":[{"given":"Zhongshi","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyun","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jconrel.2026.115409_bb0005","article-title":"Checkpoint inhibitors and beyond: a systematic review of immunotherapy in cu-taneous malignancies","volume":"17","author":"Rashid","year":"2025","journal-title":"Cureus"},{"key":"10.1016\/j.jconrel.2026.115409_bb0010","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/CM9.0000000000003416","article-title":"Recent global patterns in skin cancer incidence, mortality, and prevalence","volume":"138","author":"Wang","year":"2025","journal-title":"Chin. Med. J."},{"key":"10.1016\/j.jconrel.2026.115409_bb0015","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1512942","article-title":"Global, regional, and national burden of cu-taneous malignant melanoma from 1990 to 2021 and prediction to 2045","volume":"14","author":"Liu","year":"2024","journal-title":"Front. Oncol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0020","doi-asserted-by":"crossref","DOI":"10.3390\/ijms251810120","article-title":"Immune checkpoint in-hibitor therapy for metastatic melanoma: what should we focus on to improve the clinical outcomes?","volume":"25","author":"Hossain","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jconrel.2026.115409_bb0025","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21072367","article-title":"Modern aspects of immunotherapy with checkpoint inhibitors in melanoma","volume":"21","author":"Petrova","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jconrel.2026.115409_bb0030","first-page":"682","article-title":"Systemic rewir-ing of dendritic cells by melanoma-secreted midkine impairs immune surveillance and re-sponse to immune checkpoint blockade","volume":"6","author":"Catena","year":"2025","journal-title":"Nat. Can."},{"key":"10.1016\/j.jconrel.2026.115409_bb0035","article-title":"Immunosuppres-sive tumor microenvironment and advance in immunotherapy in melanoma bone metasta-sis","volume":"16","author":"Ma","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0040","doi-asserted-by":"crossref","DOI":"10.3390\/ph18081082","article-title":"Tumor mi-croenvironmental dynamics in shaping re-sistance to therapeutic interventions in mela-noma: a narrative review","volume":"18","author":"Turner","year":"2025","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.jconrel.2026.115409_bb0045","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1385781","article-title":"The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma-two sides of the same coin?","volume":"15","author":"Reschke","year":"2024","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0050","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3390\/ijms24010041","article-title":"Insights and strate-gies of melanoma immunotherapy: predictive biomarkers of response and resistance and strategies to improve response rates","volume":"24","author":"Seyhan","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jconrel.2026.115409_bb0055","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.ccell.2025.01.009","article-title":"Genomic mediators of acquired re-sistance to immunotherapy in metastatic mel-anoma","volume":"43","author":"Schiantarelli","year":"2025","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jconrel.2026.115409_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2025.115339","article-title":"Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study","volume":"220","author":"Weichenthal","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.jconrel.2026.115409_bb0065","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3390\/biomedicines13010225","article-title":"Advances in immunotherapy and targeted therapy of malignant melanoma","volume":"13","author":"Wang","year":"2025","journal-title":"Biomedicines"},{"key":"10.1016\/j.jconrel.2026.115409_bb0070","doi-asserted-by":"crossref","first-page":"24932","DOI":"10.18632\/oncotarget.15326","article-title":"The TLR7 agonist imiquimod induces anti-cancer effects via autophagic cell death and enhances anti-tumoral and sys-temic immunity during radiotherapy for mel-anoma","volume":"8","author":"Cho","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.jconrel.2026.115409_bb0075","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jdermsci.2022.08.006","article-title":"Imiquimod-induced ROS pro-duction causes lysosomal membrane perme-abilization and activates caspase-8-mediated apoptosis in skin cancer cells","volume":"107","author":"Chang","year":"2022","journal-title":"J. Dermatol. Sci."},{"key":"10.1016\/j.jconrel.2026.115409_bb0080","first-page":"175","article-title":"Systemic IFN-I com-bined with topical TLR7\/8 agonists promotes distant tumor suppression by c-jun-dependent IL-12 expression in dendritic cells","volume":"6","author":"Sanlorenzo","year":"2025","journal-title":"Nat. Can."},{"key":"10.1016\/j.jconrel.2026.115409_bb0085","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202503019","article-title":"An injectable hy-drogel co-delivering propranolol and imiquimod to synergistically enhance immu-nogenic cell death after melanoma resection","volume":"15","author":"Tang","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"10.1016\/j.jconrel.2026.115409_bb0090","first-page":"9542","article-title":"Novel combination treatment for melanoma: FLASH radiotherapy and immu-notherapy delivered by a radiopaque and ra-diation responsive hydrogel","volume":"35","author":"Dong","year":"2023","journal-title":"Chem. Mater.\u00a0Publ. Am. Chem. Soc."},{"key":"10.1016\/j.jconrel.2026.115409_bb0095","article-title":"Regulation of immuno-genic cell death and potential applications in cancer therapy","volume":"16","author":"Kun","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0100","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/imr.13271","article-title":"Molecular determinants of immu-nogenic cell death elicited by radiation therapy","volume":"321","author":"Claudia","year":"2024","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.jconrel.2026.115409_bb0105","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1667\/RR14177.1","article-title":"Radiation exposure promotes hepato-carcinoma cell invasion through epithelial mesenchymal transition mediated by H2S\/CSE pathway","volume":"185","author":"Pan","year":"2016","journal-title":"Radiat. Res."},{"key":"10.1016\/j.jconrel.2026.115409_bb0110","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1667\/RR2967.1","article-title":"Suppres-sion of endogenous hydrogen sulfide con-tributes to the radiation-induced bystander ef-fects on hypoxic HepG2 cells","volume":"178","author":"Zhang","year":"2012","journal-title":"Radiat. Res."},{"key":"10.1016\/j.jconrel.2026.115409_bb0115","doi-asserted-by":"crossref","unstructured":"Y. Pan, S. Ye, D. Yuan, J. Zhang, Y. Bai, C. Shao, Radioprotective role of H2S\/CSE pathway in chang liver cells, Mutat. Res. 738\u2013739 (2012) 12\u201318. doi: https:\/\/doi.org\/10.1016\/j.mrfmmm.2012.08.007.","DOI":"10.1016\/j.mrfmmm.2012.08.007"},{"key":"10.1016\/j.jconrel.2026.115409_bb0120","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1667\/RR15074.1","article-title":"Blocking endoge-nous H2S signaling attenuated radiation-induced long-term metastasis of residual HepG2 cells through inhibition of EMT","volume":"190","author":"Zhang","year":"2018","journal-title":"Radiat. Res."},{"key":"10.1016\/j.jconrel.2026.115409_bb0125","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1158\/1535-7163.MCT-15-0583","article-title":"Antagonizing the hedgehog pathway with vismodegib impairs malignant pleural mesothelioma growth in vivo by af-fecting stroma","volume":"15","author":"Meerang","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.jconrel.2026.115409_bb0130","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.chembiol.2021.05.016","article-title":"Intracellular H2S production is an autophagy-dependent adaptive response to DNA damage","volume":"28","author":"Jiang","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0135","article-title":"Mechanisms underlying radioresistance and reversal strategies in non-small cell lung can-cer","volume":"26","author":"Zhao","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jconrel.2026.115409_bb0140","doi-asserted-by":"crossref","DOI":"10.1097\/PPO.0000000000000780","article-title":"Harnessing immuno-genic cell death to boost the impact of radia-tion therapy","volume":"31","author":"Mannion","year":"2025","journal-title":"Cancer J."},{"key":"10.1016\/j.jconrel.2026.115409_bb0145","article-title":"Radiotherapy and immune microenvironment crosstalk in pancreatic cancer: a comprehensive review of current insights and future directions","volume":"16","author":"Xu","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0150","article-title":"Influence of hypoxia on tumor heterogeneity, DNA repair, and cancer therapy: from molecular insights to therapeutic strategies","volume":"14","author":"Dpminika","year":"2025","journal-title":"Cells"},{"key":"10.1016\/j.jconrel.2026.115409_bb0155","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202214992","article-title":"Tumor-selective activation of toll-like recep-tor 7\/8 agonist nano-immunomodulator gen-erates safe anti-tumor immune responses up-on systemic administration","volume":"61","author":"Hao","year":"2022","journal-title":"Angew. Chem."},{"key":"10.1016\/j.jconrel.2026.115409_bb0160","doi-asserted-by":"crossref","DOI":"10.1002\/cbic.202300155","article-title":"Stimuli-responsive prodrug chemistries for cancer therapy","volume":"24","author":"Bargakshatriya","year":"2023","journal-title":"Chembiochem"},{"key":"10.1016\/j.jconrel.2026.115409_bb0165","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrd1470","article-title":"Can the pharmaceutical industry reduce attrition rates?","volume":"3","author":"Kola","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jconrel.2026.115409_bb0170","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12916-016-0553-2","article-title":"Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature","volume":"14","author":"Onakpoya","year":"2016","journal-title":"BMC Med."},{"key":"10.1016\/j.jconrel.2026.115409_bb0175","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1039\/D4BM00647J","article-title":"Reactive oxygen species driven prodrug-based nanoscale carriers for transformative therapies","volume":"12","author":"Vasvani","year":"2024","journal-title":"Biomater. Sci."},{"key":"10.1016\/j.jconrel.2026.115409_bb0180","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ccr.2009.10.013","article-title":"Tis-sue-penetrating delivery of compounds and nanoparticles into tumors","volume":"16","author":"Kazuki N","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jconrel.2026.115409_bb0185","article-title":"Tumor-penetrating peptides","volume":"3","author":"Tambet","year":"2013","journal-title":"Front. Oncol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0190","article-title":"iRGD: a promising peptide for cancer imaging and a potential therapeutic agent for various cancers","author":"Houdong","year":"2019","journal-title":"J. Oncol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbcan.2023.188895","article-title":"Exploration of tumor penetrating peptide iRGD as a potential strategy to en-hance tumor penetration of cancer nanother-apeutics","volume":"1878","author":"Saifi","year":"2023","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"10.1016\/j.jconrel.2026.115409_bb0200","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.697964","article-title":"Immunogenic cell death-based cancer vaccines","volume":"12","author":"Jin","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0205","doi-asserted-by":"crossref","first-page":"10906","DOI":"10.1039\/D1NR02018H","article-title":"Tumor microenvi-ronment-triggered in situ cancer vaccines in-ducing dual immunogenic cell death for ele-vated antitumor and antimetastatic therapy","volume":"13","author":"Ding","year":"2021","journal-title":"Nanoscale"},{"key":"10.1016\/j.jconrel.2026.115409_bb0210","doi-asserted-by":"crossref","first-page":"21468","DOI":"10.1021\/acsnano.5c02569","article-title":"Magnetic microcarrier-based whole tumor cell vaccines for tumor prevention and immunotherapy","volume":"19","author":"Wu","year":"2025","journal-title":"ACS Nano"},{"key":"10.1016\/j.jconrel.2026.115409_bb0215","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.575597","article-title":"Localized interleukin-12 for cancer immunotherapy","volume":"11","author":"Nguyen","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0220","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1160\/th14-04-0299","article-title":"TNF-induced endothelial barrier disrup-tion: beyond actin and rho","volume":"112","author":"Marcos-Ramiro","year":"2014","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.jconrel.2026.115409_bb0225","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0297325","article-title":"Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer","volume":"19","author":"Tushoski-Alem\u00e1n","year":"2024","journal-title":"PLoS One"},{"key":"10.1016\/j.jconrel.2026.115409_bb0230","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202505250","article-title":"Passivation-engineered zinc peroxide nano-particles as Th1-biased adjuvant for anti-tumor immunity","volume":"21","author":"Luo","year":"2025","journal-title":"Small"},{"key":"10.1016\/j.jconrel.2026.115409_bb0235","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.immuni.2023.09.011","article-title":"The cancer-immunity cycle: Indica-tion, genotype, and immunotype","volume":"56","author":"Mellman","year":"2023","journal-title":"Immunity"},{"key":"10.1016\/j.jconrel.2026.115409_bb0240","article-title":"Central memory T cells: stem-like biology, pathogenic roles in autoimmunity, and therapeutic applications","author":"Dalin","year":"2026","journal-title":"Clin. Exp. Rheumatol."},{"key":"10.1016\/j.jconrel.2026.115409_bb0245","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2020.101435","article-title":"Memory CD8+ T cell responses to cancer","volume":"49","author":"Han","year":"2020","journal-title":"Semin. Immunol."}],"container-title":["Journal of Controlled Release"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365926008138?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365926008138?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:44:37Z","timestamp":1793439877000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168365926008138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":49,"alternative-id":["S0168365926008138"],"URL":"https:\/\/doi.org\/10.1016\/j.jconrel.2026.115409","relation":{},"ISSN":["0168-3659"],"issn-type":[{"value":"0168-3659","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Radiotherapy-ignited dual-stage prodrug nanoplatform for cascade activation of toll-like receptor 7\/8 agonist and reignition of antitumor immunity","name":"articletitle","label":"Article Title"},{"value":"Journal of Controlled Release","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jconrel.2026.115409","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115409"}}