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While its effectiveness is ultimately limited by patient heterogeneity and immunosuppressive tumor microenvironment. Photodynamic therapy (PDT), as an emerging antitumor immunotherapy, has shown its unique therapeutic advantages. However, previous studies often overlooked the potential toxicity of photosensitizers (PS), making the discovery of safe and effective PS\u00a0a pressing clinical need. In this study, Aloe Emodin (AE), a medicinal plant natural compound, was loaded with copper ions\u00a0(Cu), and self\u2010assembled into nanoparticles (NPs) under the modification of PEG<jats:sub>2k<\/jats:sub>\u2010DSPE\u2010FA. NPs can target, accumulate, and reside within tumor sites, responsively releasing copper ions and AE, thus dual\u2010functioning by inducing tumor cell death via cuproptosis and enhancing PDT effects. The LLC tumor\u2010bearing mouse model demonstrated that NPs induce the maturation of dendritic cells (DCs) in vivo, promote lymphocyte infiltration, transform\u00a0\u201ccold tumors\u201d into \u201chot tumors\u201d and significantly enhance the efficacy of immune checkpoint blockade (ICB). This study provides experimental evidence of AE as a clinically promising PDT agent and offers a novel perspective for the synergistic treatment of clinical NSCLC.<\/jats:p>","DOI":"10.1002\/adhm.202404612","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T01:14:07Z","timestamp":1740532447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Inducing Cuproptosis with Copper Ion\u2010Loaded Aloe Emodin Self\u2010Assembled Nanoparticles for Enhanced Tumor Photodynamic Immunotherapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Zhen","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmacy Xiangya Hospital Central South University  Changsha Hunan 410008 P. R. China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha 410008 P. R. 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