Inorganic Nanobiomaterials Boost Tumor Immunotherapy: Strategies and Applications

ConspectusTumor immunotherapy, as a new antitumor method to fight cancer by activating or enhancing the body's own immune system, has been extensively studied and applied in clinical practice. However, as an extremely complex system, tumor heterogeneity and complex immunosuppressive tumor microenvironment (TME) lead to poor immune response rate or secondary drug resistance. The advent of nanotechnology has ushered in a new era for immunotherapy. In particular, inorganic nanomaterials, with their unique physicochemical properties and excellent biocompatibility, are becoming an important tool for enhancing immunotherapy. Inorganic nanomaterials can be used as carriers for immune agents, improving drug delivery efficiency and thereby reducing systemic immunotoxicity and enhancing immune responses. Inorganic nanomaterials also trigger tumor immunogenic cell death (ICD), stimulate antitumor immune responses, and alleviate immunosuppressive TME by increasing oxygen levels, modulating metabolic pathways, and altering the secretion of immunosuppressive cytokines. The synergistic integration of inorganic nanomaterials with immunotherapy adeptly navigates around the constraints of conventional treatments, reducing side effects while concurrently augmenting therapeutic efficacy. In this review, we summarize our recent efforts in the design and synthesis of inorganic nanobiomaterials to enhance the efficacy of tumor immunotherapy. These nanomaterials achieve the desired immune efficacy mainly through four strategies, including inducing ICD, developing tumor nanovaccines, activating pyroptosis, and regulating tumor metabolism, providing beneficial implications for tumor immunotherapy. For one thing, due to the deficiency of ICD effect in single therapy, we mainly developed nanocatalysts that integrate multiple therapeutic functions to play a catalytic role in TME, converting tumor substances or metabolites into therapeutic products in situ, and further enhancing ICD. For another, in order to solve the problems of low antigen loading and therapeutic efficiency of existing adjuvants, several novel multifunctional nanoadjuvants were prepared, which combine high antigen loading and multimode therapeutic function in one, and achieve efficient immune activation. Moreover, to attain strong inflammatory responses and immunogenicity, we engineer pyroptosis adjuvants that selectively induce tumor cell pyroptosis by enhancing intracellular oxidative stress or ion overload. Finally, to reverse the immunosuppressive microenvironment, we developed nanoplatforms that target tumor metabolism, altering the levels of nutrients and metabolites in tumor such as glucose, lactic acid, citric acid, and tryptophan to effectively alter the TME, thereby activating and enhancing the body's immune response. The implementation of these strategies not only improves the therapeutic effect but also reduces the side effects and provides valuable insights and references for the development of novel nanomaterials to assist immunotherapy.