Biomedical nanomaterials for the enhancement of immunogenic cell death-based cancer immunotherapy

The activation of adaptive antitumor immune response is paramount for improving the long-term antitumor efficiency. Chemotherapy, radiotherapy, and photodynamic therapy (PDT) can induce cell apoptosis and immunogenic cell death (ICD). Subsequently, the exposure or release of damage-associated molecular patterns (DAMPs) caused by ICD can stimulate the immune system to exert an antitumor immune response, recruit the antigen-presenting cells, and activate the adaptive immune responses of T cells. As such, the application of ICD inducers in tumor therapy is of crucial role in improving the therapeutic effects and the survival rate of cancer patients. Recently, accumulating evidence has revealed that nanomaterials-based platforms for cancer treatment could not only achieve controlled drug release in response to stimulation of tumor microenvironment (TME), but also regulate TME to enhance ICD in the tumor. Hence, the construction of ICD effects-based biomedical nanomaterials has sparked tremendous attention. Benefiting from their unique size, biomedical nanomaterials are commonly applied as ICD inducers carriers to target tumor tissue and enhance selective enrichment in the tumor. By taking advantage of their easily modified surface properties and multi-selectivity of raw materials, nanomaterials can also be designed as functionalized carriers with stimulus responses to TME, thereby achieving stepwise and controlled release of ICD inducers. Meanwhile, biomedical nanomaterials are capable of codelivering different components, protecting the payload from degradation and precise controlled release. These abilities enable nanomaterials to amplify the antitumor effects of chemotherapy, radiotherapy, PDT and many other emerging therapies. Of note, a single therapy has been limited by many factors. Chemotherapy and radiotherapy can bring about irreversible damage to normal tissue cells and immune cells. The hypoxic TME limits the function of PDT. On top of that, monotherapy has been also vulnerable to tumor heterogeneity. On this ground, combination therapy has become the prior option for cancer therapy. Furthermore, the synergistic of these therapies with immune checkpoints, immunosuppressive factors, immune adjuvants, immune cells and other strategies that can enhance ICD has been extensively estimated. In this paper, we first introduced the generation of the ICD, then emphasized the multifunctional roles of nanomaterials in inducing ICD and regulating the microenvironment of tumor cells. Ulteriorly, the tremendous potential, challenges and development trends of nanomaterials in therapeutic effects of ICD have been expounded and concluded. Finally, to make better use of nanomaterials and accelerate clinical transformation in the future, it is imperative to further explore the transfer efficiency, degradation and metabolism of nanomaterials, and propose a more specific and in-depth understanding of the molecular mechanism of ICD.