Abstract
AbstractMelanoma, a malignant skin tumor, presents significant treatment challenges, particularly in unresectable and metastatic cases. While immune checkpoint inhibitors (ICIs) targeting PD‐1/PD‐L1 have brought new hope, their efficacy is limited by low response rates and significant immune‐mediated adverse events (irAEs). Through multi‐omics data analysis, it is discovered that the spatial co‐localization of CD73 and PD‐L1 in melanoma correlates with improved progression‐free 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‐delivery of aPD‐L1 and APCP, a CD73 inhibitor. These nanoparticles, constructed via a biomineralization method, exhibit high drug‐loading capacity and pH‐responsive drug release. Compared to free aPD‐L1, the CaP‐delivered aPD‐L1 effectively avoids systemic side effects while significantly enhancing anti‐tumor efficacy, surpassing even a 20‐fold dose of free aPD‐L1. Furthermore, the co‐delivery of aPD‐L1 and APCP via CaP nanoparticles demonstrates a synergistic anti‐tumor effect, with substantial immune activation and prevention of tumor recurrence through immune memory effects. These findings suggest that the co‐delivery of aPD‐L1 and APCP using CaP nanoparticles is a promising approach for improving melanoma immunotherapy, achieving enhanced efficacy and reduced toxicity.
Published Version
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