Design Strategies for Hyaluronic Acid-based Drug Delivery Systems in Cancer Immunotherapy

Despite its robust therapeutic potential, cancer immunotherapy has provided little progress towards improved survival rates for patients bearing immunologically refractory tumors. The implementation of advanced drug delivery systems represents a powerful means of improving cancer immunotherapy by relieving immunosuppression and promoting immune response; however, the overall impact of these systems on immunotherapy currently remains modest. Hyaluronic acid represents a widely used polymer in drug delivery; meanwhile, recent studies linking hyaluronic acid to the immune system make this polymer an attractive component in the design of next-generation cancer immunotherapies. Herein, we review our current understanding of the immunological properties of hyaluronic acid and discuss them in the context of bioactive functions and immune-related interactions with receptors, immune, and cancer cells. We analyze the potential of hyaluronic acid as a component in advanced drug delivery systems, highlighting strategies for the design of more effective vaccines and cancer chemo-immunotherapies. Finally, we discuss critical considerations to facilitate design and clinical translation to overcome existing challenges and maximize therapeutic potential.