{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:45:40Z","timestamp":1792421140439,"version":"4.5.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82022033;82403008"],"award-info":[{"award-number":["82022033;82403008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lactic acid (LA) itself and the LA\u2010shaped acidic tumor microenvironment (TME) are identified as root causes of cancer immunosuppression, and no effective strategies address them. Here a multichannel immune nanoregulator is engineered to dampen acidic TME and repolarize non\u2010inflammatory macrophages to uproot this source of cancer immunosuppression, wherein fluorocarbon chains (FC)\u2010modified mesoporous silica (FM) serves as nanoreactors and carriers to in situ synthesize CaO\n                    <jats:sub>2<\/jats:sub>\n                    and load R848, respectively, followed by liposome coating, anti\u2010CD105 modification and FC\u2010mediated O\n                    <jats:sub>2<\/jats:sub>\n                    binding in sequence. Both liposome shell and intraparticle FC ensure safe CaO\n                    <jats:sub>2<\/jats:sub>\n                    delivery. Ultrasound\u2010triggered FC\u2010binding O\n                    <jats:sub>2<\/jats:sub>\n                    burst and liposomes\u2010destruction\u2010enhanced CaO\n                    <jats:sub>2<\/jats:sub>\n                    reactions with H\n                    <jats:sup>+<\/jats:sup>\n                    and H\n                    <jats:sub>2<\/jats:sub>\n                    O produce O\n                    <jats:sub>2<\/jats:sub>\n                    . This process depletes pre\u2010existing H\n                    <jats:sup>+<\/jats:sup>\n                    and inhibits glycolysis LA production to cut off acidic TME source, and uproots their actions in reshaping cancer immunosuppression, e.g., removing the polarization impetus toward non\u2010inflammatory M2 ones, addressing both symptoms and root causes of cytotoxic T lymphocytes and PD1+ T cells inactivation, etc. The cancer immunosuppression uprooting encourages the anti\u2010tumor efficacy of cancer calcification and intratumoral H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    accumulation in the immune nanoregulators especially after anti\u2010CD105\u2010mediated active targeting accumulation. Collectively, this work presents a solution to uproot LA and non\u2010inflammatory macrophages\u2010induced cancer immunosuppression.\n                  <\/jats:p>","DOI":"10.1002\/adma.202512230","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T11:40:18Z","timestamp":1758886818000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Multichannel Immune Nanoregulators Suppress Lactic Acid Metabolism and Lactic Acid\u2010Shaped Acidic Microenvironment to Uproot Anti\u2010Tumor Immunosuppression"],"prefix":"10.1002","volume":"38","author":[{"given":"Chao","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"},{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute School of Medicine Tongji University  No. 507, Zheng\u2010min Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Li","sequence":"additional","affiliation":[{"name":"Cancer Center Department of Ultrasound Medicine Zhejiang Provincial People's Hospital (Affiliated People's Hospital Hangzhou Medical College)  No. 158, Shangtang Road Hangzhou Zhejiang 310014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery  China. No. 17 Lujiang Road, Luyang District Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binxu","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujia","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute School of Medicine Tongji University  No. 507, Zheng\u2010min Road Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Sun","sequence":"additional","affiliation":[{"name":"Cancer Center Department of Ultrasound Medicine Zhejiang Provincial People's Hospital (Affiliated People's Hospital Hangzhou Medical College)  No. 158, Shangtang Road Hangzhou Zhejiang 310014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-1164","authenticated-orcid":false,"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-13-89"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122662"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.01.010"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00280-x"},{"key":"e_1_2_9_5_1","first-page":"916","volume":"60","author":"Walenta S.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0127"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2015.08.004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218363"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03045-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.01.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03326-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0226-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1256"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1867"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2528"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082173"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal3604"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.169"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0299-0"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301638"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202406378"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53392-1"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202406662"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202409378"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60448-3"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53010-0"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00254-0"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.05.022"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmatsci.2023.101230"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202203921"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40820-024-01533-y"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0258-0"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.003"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123100"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102038"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2019.06.003"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201701621"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.12.018"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202213729"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01752-8"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-018-0236-8"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902137"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202203106"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202403251"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01613-5"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.02.022"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4478"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b08225"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2022.136030"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.026054"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-01144-4"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202308439"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120431"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002408"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202512230","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202512230","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202512230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:58:51Z","timestamp":1768391931000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202512230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/adma.202512230"],"URL":"https:\/\/doi.org\/10.1002\/adma.202512230","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"2025-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12230"}}