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However, synthetic STING agonists like 4\u2010(5,6\u2010dimethoxybenzo[b]thiophen\u20102\u2010yl)\u20104\u2010oxobutanoic acid (MSA\u20102) exhibit suboptimal pharmacokinetics and fail to sustain STING activation in tumors for effective antitumor responses. Here, we report the design of MOF\/MSA\u20102, a bifunctional MSA\u20102 conjugated nanoscale metal\u2013organic framework (MOF) based on Hf\n                    <jats:sub>6<\/jats:sub>\n                    secondary building units (SBUs) and hexakis(4\u2032\u2010carboxy[1,1\u2032\u2010biphenyl]\u20104\u2010yl)benzene bridging ligands, for potent cancer radio\u2010immunotherapy. By leveraging the high\u2010Z properties of the Hf\n                    <jats:sub>6<\/jats:sub>\n                    SBUs, the MOF enhances the therapeutic effect of X\u2010ray radiation and elicits potent immune stimulation in the tumor microenvironment. MOF\/MSA\u20102 further enhances radiotherapeutic effects of X\u2010rays by enabling sustained STING activation and promoting the infiltration and activation of immune cells in the tumors. MOF\/MSA\u20102 plus low\u2010dose X\u2010ray irradiation elicits strong STING activation and potent tumor regression, and when combined with an immune checkpoint inhibitor, effectively suppresses both primary and distant tumors through systemic immune activation.\n                  <\/jats:p>","DOI":"10.1002\/anie.202417027","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T22:21:51Z","timestamp":1728339711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Bifunctional Metal\u2013Organic Framework Synergistically Enhances Radiotherapy and Activates STING for Potent Cancer Radio\u2010Immunotherapy"],"prefix":"10.1002","volume":"64","author":[{"given":"Chaoyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"},{"name":"Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research The University of Chicago  5758 S Maryland Ave Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"},{"name":"Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research The University of Chicago  5758 S Maryland Ave Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyao","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"},{"name":"Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research The University of Chicago  5758 S Maryland Ave Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langston","family":"Tillman","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph R.","family":"Weichselbaum","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research The University of Chicago  5758 S Maryland Ave Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7035-7759","authenticated-orcid":false,"given":"Wenbin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  929 E 57th St Chicago IL 60637 USA"},{"name":"Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research The University of Chicago  5758 S Maryland Ave Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202206370"},{"key":"e_1_2_8_2_1","unstructured":"\u00a0"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado0082"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2016.02.002"},{"key":"e_1_2_8_5_2","volume":"9","author":"Olivares-Urbano M. 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