Engineered anti-cancer nanomedicine for synergistic ferroptosis-immunotherapy

Immunotherapy has been widely used in clinical practice, but the therapeutic effects on many cancers are still poor, possibly because some patients are not sensitive to immunotherapy owing to dose-limiting immune re-sponses. Therefore, there is an urgent need for the selective amplification of the immune response during cancer therapy. Ferroptosis is a non-apoptotic programmed cell death process that can eradicate tumors through reactive oxygen accumulation and iron-dependent pathways. It is highly dependent on the tumor microenvi-ronment, which provides a new opportunity for selectively triggering tumor immunity to overcome tumors. In addition, antitumor immune responses can be amplified through multiple mechanisms, thereby increasing the sensitivity of tumor cells to immunotherapy. Therefore, the combination of ferroptosis and immunotherapy in cancer nanomedicine offers the possibility of eradicating tumors in a safe and effective manner. This review summarizes various engineered nanomaterials for synergistic cancer ferroptosis immunotherapy, including metal oxides, metal-organic frameworks, single metal elements, FePt, ferrous hydrates, endogenous iron substances, liposomes, and polymers. With particular emphasis on the mechanism by which these nanomedicines can improve ferroptosis in tumor cells and mediate antitumor immunity by activating the tumor immune microen-vironment relationship, as well as their application prospects and evaluation of challenges in future cancer treatment, we aim to further promote the development of ferroptosis immunotherapy-based nanomedicine from basic scientific research to clinical transformation.