Harnessing biomaterial architecture to drive anticancer innate immunity

Immunomodulation is a powerful therapeutic approach that harnesses the body's own immune system and reprograms it to treat diseases, such as cancer. Innate immunity is key in mobilizing the rest of the immune system to respond to disease and is thus an attractive target for immunomodulation. Biomaterials have widely been employed as vehicles to deliver immunomodulatory therapeutic cargo to immune cells and raise robust antitumor immunity. However, it is key to consider the design of biomaterial chemical and physical structure, as it has direct impacts on innate immune activation and antigen presentation to stimulate downstream adaptive immunity. Herein, we highlight the widespread importance of structure-driven biomaterial design for the delivery of immunomodulatory cargo to innate immune cells. The incorporation of precise structural elements can be harnessed to improve delivery kinetics, uptake, and the targeting of biomaterials into innate immune cells, and enhance immune activation against cancer through temporal and spatial processing of cargo to overcome the immunosuppressive tumor microenvironment. Structural design of immunomodulatory biomaterials will profoundly improve the efficacy of current cancer immunotherapies by maximizing the impact of the innate immune system and thus has far-reaching translational potential against other diseases.