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Herein, uniform CaCO\n                    <jats:sub>3<\/jats:sub>\n                    nanoparticles encapsulated nickel\u2013alginate microspheres (CaNPs\/Ni\u2010Alg MSs) were engineered using a microfluidic device, serving as an immune\u2010regulated embolic agent to amplify TAE treatment of HCC. CaNPs\/Ni\u2010Alg MSs could adsorb His\u2010tagged interleukin\u20102 (IL\u20102) and enable sustained release through coordination interactions between the His\u2010tag and Ni\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , thereby reducing systemic cytokine elevation risk from IL\u20102 administration. IL\u20102\u2010loaded microspheres (IL\u20102\/CaNPs\/Ni\u2010Alg MSs) effectively neutralize intratumoral lactic acid (LA) via CaCO\n                    <jats:sub>3<\/jats:sub>\n                    , modulating the acidic TME. Proton neutralization restores IL\u20102 activity, enhancing T lymphocyte infiltration and proliferation. Additionally, lactate made available following acid neutralization may serve as a metabolic substrate, as supported by the calcium lactate and neutralization\u2010mimicking experiments in vitro, contributing to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell metabolic fitness. IL\u20102\/CaNPs\/Ni\u2010Alg MSs could reprogram the TME into an immune\u2010promoting milieu, synergizing with immune checkpoint blockade (ICB) therapy to suppress both primary and distant tumors. Not surprisingly, TAE with IL\u20102\/CaNPs\/Ni\u2010Alg MSs combined with \u03b1PD\u2010L1 achieved superior therapeutic efficacy without side effect in a rat orthotopic HCC model. Overall, this work presents a safe metabolism\u2010reprogramming embolic strategy that repurposes LA to boost IL\u20102\u2013mediated embolization\u2010immunotherapy in HCC.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71749","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:53:34Z","timestamp":1790139214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactate\u2010Weaponized Microspheres Amplify IL\u20102\u2013Driven Immuno\u2010Embolization for Hepatocellular Carcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1246-6522","authenticated-orcid":false,"given":"Minjiang","family":"Chen","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Imaging and Interventional Medicine Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical 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