Recently, Professor Li Suxin from our university's School of Pharmacy collaborated with the team of Academician Zhang Qiang from Peking University to publish a review paper titled “Metallic Nanomedicine in Cancer Immunotherapy” in the top-tier journal Acta Pharmaceutica Sinica B. China Pharmaceutical University is listed as the first corresponding institution, with graduate students Li Shixuan and Wang Xiaohu from our School of Pharmacy serving as first authors.
From the efficacy of cinnabar (mercury sulfide) in calming the mind and alleviating anxiety as described in the Divine Farmer's Classic of Materia Medica, to the use of arsenic trioxide (arsenic trioxide) for treating masses and accumulations in the Compendium of Materia Medica, and the modern clinical applications of arsenic trioxide and cisplatin, the concepts and wisdom of metal-based therapies in traditional Chinese medicine are undergoing a rebirth from empirical practices to scientific forms. In recent years, the pivotal role of metallic elements in regulating antitumor immune processes has gained recognition. For instance: manganese, as an immunological adjuvant, activates the cGAS-STING signaling pathway to transform the tumor microenvironment from “cold” to ‘hot’; elements like iron and copper induce novel cancer cell death mechanisms—ferroptosis or cupric-mediated death—signaling to the immune system to “eat me.” When combined with nanotechnology, the physicochemical properties of metal elements can be further optimized, enabling precise spatiotemporal regulation of in vivo delivery and release behavior to enhance drugability. Several metal nanomedicines with immunotherapeutic potential have now entered various stages of clinical trials.
Against this backdrop, this paper systematically reviews the molecular mechanisms by which metal elements exert immunomodulatory effects across diverse cell types. It summarizes recent advances in integrating metals as drugs or carriers into smart nanodelivery systems to enhance tumor immunotherapy, outlines the current clinical status of metallic nanomedicines in immunotherapy, and discusses potential challenges in clinical translation, including large-scale production and long-term biosafety. Looking ahead, metal-based immunotherapies hold promise when combined with advanced technologies such as immunomics and artificial intelligence, driving more precise and personalized approaches to cancer treatment.
Original link: https://doi.org/10.1016/j.apsb.2025.07.017
