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However, conventional X\u2010PDT typically relies on heavy metal inorganic scintillators and organic photosensitizers to produce\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , which presents challenges related to toxicity and energy conversion efficiency. In this study, highly biocompatible organic phosphorescent nanoscintillators based on hydrogen\u2010bonded organic frameworks (HOF) are designed and engineered, termed BPT\u2010HOF@PEG, to enhance X\u2010PDT in hepatocellular carcinoma (HCC) treatment. BPT\u2010HOF@PEG functions simultaneously as both scintillator and photosensitizer, effectively absorbing and transferring X\u2010ray energy to generate abundant\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . Both in vitro and in vivo investigations demonstrate that internalized BPT\u2010HOF@PEG efficiently produces significant quantities of\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    upon X\u2010ray irradiation. Additionally, X\u2010ray exposure directly inflicts DNA damage, and the synergistic effects of these mechanisms result in pronounced cell death and substantial tumor growth inhibition, with a significant inhibition rate of up to 90.4% in vivo assessments. RNA sequencing analyses reveal that X\u2010PDT induces apoptosis in Hepa1\u20106 cells while inhibiting cell proliferation, culminating in tumor cell death. Therefore, this work highlights the considerable potential of efficient phosphorescent HOF nanoscintillators\u2010based X\u2010PDT as a promising therapeutic approach for HCC, providing a highly effective alternative with negligible toxicity for patients with unresectable tumors.\n                  <\/jats:p>","DOI":"10.1002\/adma.202417001","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T02:13:34Z","timestamp":1736561614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hydrogen\u2010Bonded Organic Framework Nanoscintillators for X\u2010Ray\u2010Induced Photodynamic Therapy in Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"37","author":[{"given":"Lihui","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery Hospital Naval Medical University  Shanghai 200438 P. R. 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