Pathological angiogenesis and immunosuppression limit the efficacy of cancer treatment. This study reports a biomimetic nanoparticle platform that integrates a targeted vascular endothelial growth factor receptor 2 (VEGFR2) with a tumor cell membrane coating. Phenotypic screening identified tetrafluoroethane [4-(amino)piperidin-1-yl]C60 cycloepoxide (TAPC) as a potent inhibitor of angiogenesis. Transcriptomic analysis confirmed that VEGFR2 is a highly expressed and clinically relevant target in colorectal cancer (CRC), prompting further mechanistic studies. It was found that TAPC can target VEGFR2, reduce its expression, and inhibit the PI3K-AKT signaling in tumors and endothelial cells. To enhance delivery, TAPC was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles and coated with the same tumor cell membrane to generate tumor cell membrane-encapsulated nanoparticles (TAPC@CNPs). This formulation increased stability, supported systemic circulation, and promoted tumor accumulation. In a mouse CRC model, TAPC@CNPs significantly inhibited tumor growth and reduced angiogenesis markers, including VEGFR2 and CD31. Moreover, treatment reduced the level of regulatory T cells, increased T cell infiltration and activation, indicating enhanced anti-tumor immunity. These findings established TAPC as a fullerene-based VEGFR2 inhibitor and demonstrated that tumor membrane-encapsulated nanoparticle delivery enhances its anti-angiogenic and immunomodulatory effects, providing a nanomaterial strategy that can simultaneously target angiogenesis and remodel the tumor immune microenvironment. This study was published in Bioactive Materials under the title "Aminated fullerene-based nanoplatform enables synergistic VEGFR2-targeted anti-angiogenesis and tumor immunotherapy".
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DOI: 10.1016/j.bioactmat.2026.03.016