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Meanwhile, after radiotherapy (RT), the programmed death ligand\u20101 (PD\u2010L1) overexpression and transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi\u2010immune pathway regulation strategy through PD\u2010L1, collagen, and TGF\u2010\u03b2 co\u2010depression. Then, IR\u2010LND is prepared by combining the mitochondria\u2010targeted molecule IR\u201068 with LND, which then is loaded with liposomes (Lip) to create IR\u2010LND@Lip nanoadjuvants. By doing this, IR\u2010LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD\u2010L1, collagen, and TGF\u2010\u03b2 co\u2010inhibition. In conclusion, the combined treatment of RT and IR\u2010LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.<\/jats:p>","DOI":"10.1002\/advs.202400297","type":"journal-article","created":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T05:49:10Z","timestamp":1714888150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Mitochondria\u2010Targeted Nanoadjuvants Induced Multi\u2010Functional Immune\u2010Microenvironment Remodeling to Sensitize Tumor Radio\u2010Immunotherapy"],"prefix":"10.1002","volume":"11","author":[{"given":"Zaigang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Urology The Third Xiangya Hospital of Central South University  Changsha 410013 China"},{"name":"National Engineering Research Center of Ophthalmology and Optometry Eye Hospital Wenzhou Medical University  Wenzhou Zhejiang 325027 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