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Incredibly, intracellular PD\u2010L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD\u2010L1function still limits the effectiveness of radio\u2010immunotherapy. Therefore, better PD\u2010L1 regulation strategies are still urgently needed to better sensitize radio\u2010immunotherapy. Hence, for this purpose, TPP\u2010LND is synthesized by linking mitochondrial\u2010targeted triphenylphosphine cations (TPP<jats:sup>+<\/jats:sup>) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300\u00a0\u00b5<jats:sc>M<\/jats:sc>). Then, TPP\u2010LND is wrapped with liposomes to form TPP\u2010LND@Lip nanoparticles. By doing this, TPP\u2010LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD\u2010L1 via enhancing the adenosine 5\u2032\u2010monophosphate\u2010activated protein kinase activation.\u00a0As expected, these well\u2010designed economical TPP\u2010LND@Lip nanoparticles are more effective than conventional anti\u2010PD\u2010L1 antibodies to some extent.<\/jats:p>","DOI":"10.1002\/advs.202207608","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T06:30:24Z","timestamp":1682317824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Metabolic Intervention Liposome Boosted Lung Cancer Radio\u2010Immunotherapy via Hypoxia Amelioration and PD\u2010L1 Restraint"],"prefix":"10.1002","volume":"10","author":[{"given":"Saijun","family":"Wang","sequence":"first","affiliation":[{"name":"Medical 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Key Laboratory of Basic Science and Translational Research of Radiation Oncology  Wenzhou Zhejiang 325000 China"},{"name":"Zhejiang\u2010Hong Kong Precision Theranostics of Thoracic Tumors Joint Laboratory The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang 325000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041259"},{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-020-00407-5"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01450-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13870"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20190524"},{"key":"e_1_2_10_4_2","first-page":"883","volume":"24","author":"Tsoukalas M. 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