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Herein, a carbonic anhydrase inhibitor (CAI) is loaded onto pH\u2010responsive calcium carbonate (CaCO\n                    <jats:sub>3<\/jats:sub>\n                    ) nanoparticles and then modify theses nanoparticles with liposomes to obtain biocompatible CaCO\n                    <jats:sub>3<\/jats:sub>\n                    \/CAI@Lipsome (CCL) for enhance tumor radio\u2010immunotherapy. CCL can specially decompose in tumor microenvironment, releasing calcium ion (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) and CAI, as well as increasing the pH value of extracellular fluid. CAI restrains the flow of hydrogen ion (H\n                    <jats:sup>+<\/jats:sup>\n                    ) inside and outside the tumor cells, resulting in the reversal of tumor acidic microenvironment and the increase of intracellular H\n                    <jats:sup>+<\/jats:sup>\n                    , both of which can improve the sensitivity of tumor to radiotherapy. Afterward, the increased intracellular H\n                    <jats:sup>+<\/jats:sup>\n                    together with radiotherapy\u2010causes reactive oxygen species promotes calcium influx, leading to cellular calcium overload. Moreover, the CCL\u2010tailored content of H\n                    <jats:sup>+<\/jats:sup>\n                    and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    strengthens radiotherapy\u2010induced immunogenic cell death and dendritic cell maturation, amplifying systemic anti\u2010tumor adaptive immunity. Meanwhile, macrophages in the CCL\u2010treated tumors are polarized from pro\u2010tumor M2 to anti\u2010tumor M1 under X\u2010ray exposure, owing to the neutralization of tumor acidic microenvironment and enhances Ca\n                    <jats:sup>2+<\/jats:sup>\n                    content. Therefore, multi\u2010directional regulation of the intra\/extra tumor cell pH\/calcium by simple nano\u2010preparation would provide a powerful way to improve the efficacy of radio\u2010immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202304092","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:36:58Z","timestamp":1695429418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Regulation of Ion Homeostasis for Enhanced Tumor Radio\u2010Immunotherapy"],"prefix":"10.1002","volume":"10","author":[{"given":"Rui","family":"Qian","sequence":"first","affiliation":[{"name":"Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine Southern Medical University  Guangzhou 510000 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