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While immune checkpoint inhibitors (ICIs) targeting PD\u20101\/PD\u2010L1 have brought new hope, their efficacy is limited by low response rates and significant immune\u2010mediated adverse events (irAEs). Through multi\u2010omics data analysis, it is discovered that the spatial co\u2010localization of CD73 and PD\u2010L1 in melanoma correlates with improved progression\u2010free survival (PFS), suggesting a synergistic potential of their inhibitors. Building on these insights, a novel therapeutic strategy using calcium phosphate (CaP) nanoparticles is developed for the co\u2010delivery of aPD\u2010L1 and APCP, a CD73 inhibitor. These nanoparticles, constructed via a biomineralization method, exhibit high drug\u2010loading capacity and pH\u2010responsive drug release. Compared to free aPD\u2010L1, the CaP\u2010delivered aPD\u2010L1 effectively avoids systemic side effects while significantly enhancing anti\u2010tumor efficacy, surpassing even a 20\u2010fold dose of free aPD\u2010L1. Furthermore, the co\u2010delivery of aPD\u2010L1 and APCP via CaP nanoparticles demonstrates a synergistic anti\u2010tumor effect, with substantial immune activation and prevention of tumor recurrence through immune memory effects. These findings suggest that the co\u2010delivery of aPD\u2010L1 and APCP using CaP nanoparticles is a promising approach for improving melanoma immunotherapy, achieving enhanced efficacy and reduced toxicity.<\/jats:p>","DOI":"10.1002\/advs.202410545","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T04:05:50Z","timestamp":1735013150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Co\u2010Delivery of aPD\u2010L1 and CD73 Inhibitor Using Calcium Phosphate Nanoparticles for Enhanced Melanoma Immunotherapy with Reduced Toxicity"],"prefix":"10.1002","volume":"12","author":[{"given":"Peng","family":"Liu","sequence":"first","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan 410013 China"},{"name":"Department of Nuclear Medicine Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"Key Laboratory 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