Biological effects of metal-based nanomaterials for tumor metalloimmunotherapy

Tumor immunotherapy as a new tumor therapy has been intensively studied and reported. However, the expected utilization and therapeutic effects have not been achieved due to the large individual differences among patients. Recently, the role of metal ions in immunotherapy has been extensively studied. Therefore, it has become an effective means to design metal-based nanomaterials and deliver them to the tumor site to enhance immunotherapy by using metal-based nanomaterials themselves or the composition of metal ions they release to regulate immune responses, namely, metalloimmunotherapy. In this review, we summarized the applications of metal-based nanomaterials in tumor metalloimmunotherapy based on their unique biological effects, mainly including the following directions: 1) metal-based nanomaterial-induced ferroptosis; 2) metal-based nanomaterial-induced immunogenic cell death; 3) metal-based nanomaterial-induced pyroptosis; 4) metal-based nanomaterial-induced programmed necroptosis; 5) metal-based nanomaterials induce other death modes; 6) metal-based nanomaterial activated or inhibited autophagy; and 7) metal-based nanomaterial activation of the cGAS-STING pathway. Meanwhile, the shortcomings of metal-based nanomaterials in enhancing metalloimmunotherapy are also discussed and prospected, and this timely review based on metalloimmunotherapy provides a new direction in cancer immunotherapy.