Melanoma MHC-I-membrane-encapsulated Cu@ferrihydrite induces ferroptosis/cuproptosis and systematic immunity against tumor.

作者：Rong Yang, Fangqing Deng, Zibo Gao, Xu Li, Shuaiqi Huangfu, Qing Tian, Haoyu Wang, Huifang Liu, Xuejing Wang, Yao Chen, Yingchun Yang, Genyang Cheng, Lianbing Zhang · 发表于：Journal of Controlled Release · 年份：2025 · DOI：10.1016/j.jconrel.2025.114281 · 被引用次数：8 · 研究领域：Medicine

Major histocompatibility complex I (MHC-I) has significant potential for augmenting cancer immunogenicity and immune recognition. Here, we report an innovative therapeutic strategy that synergistically integrates blue light-upregulated MHC-I expression with blue light-induced ferroptosis and cuproptosis. Blue light promoted MHC-I expression in mouse melanoma cells by modulating the NF-κB-SUSD6 signaling axis. Subsequently, an MHC-I-enriched melanoma cytomembrane was used to encapsulate the photoresponsive Cu@ferrihydrite (Cu@Fh) nanoparticles, forming M-Cu@Fh. MHC-I facilitated dendritic cells (DCs) maturation and CD8+/CD4+ T cells activation. M-Cu@Fh also triggered oxidative stress and concurrent ferroptosis/cuproptosis through the controllable release of Fe/Cu ions under blue-light irradiation. In vivo experiments demonstrated that the combination of blue light and M-Cu@Fh converted immune "cold" tumors into "hot" tumors, suppressed in situ melanoma growth through oxidative damages and enhanced immunogenicity. Furthermore, systemic activation of DCs and CD8+/CD4+ T cells in lymphoid organs (lymph nodes and spleen) and lungs conferred prophylactic efficacy against abscopal metastasis. Our study elucidates the photoregulatory mechanism of MHC-I in melanoma cells and presents a transformative combinatorial strategy that synergizes blue light-driven photoimmunotherapy (PIT) with blue light-activated photodynamic therapy (PDT) for melanoma management and metastasis prevention.