Nanomaterials-mediated adenosine pathway inhibition for strengthening cancer immunotherapy

Immunotherapy has developed into an attractive tumor treatment strategy. However, the existence of an immunosuppressive tumor microenvironment (ITME) greatly reduces the efficacy of immunotherapy. Adenosine (ADO) is one of the vital negative feedbacks in ITME, which inhibits antigen presentation and immune cell activation by binding to adenosine receptors (ADORs), thus tremendously suppressing immune response. Currently, the treatment effect of numerous inhibitors targeting the ADO pathway has been demonstrated in early clinical trials of various tumors. Nevertheless, the clinical application of these inhibitors is still plagued by diverse issues, such as short half-life, a single administration route, low bioavailability, etc. With the progress of nanotechnology, the delivery system of ADO inhibitors based on nanomaterials can solve the above problems. This review discusses the utilization of nanomaterials as a prospective method to inhibit ADO pathway and enhance immunotherapy outcomes. Specifically, the immunosuppressive mechanisms of ADO are summarized, and the corresponding intervention strategies are proposed. Then plentiful nanomaterials targeting the ADO pathway are highlighted, including phospholipids and polymers-based nanomaterials, mesoporous nanomaterials, biomimetic nanomaterials and metal-based nanomaterials. Finally, the outlook and challenges about nanomaterials-mediated ADO pathway inhibition were outlined, expecting to promote the clinical application of ADO inhibitor nanomedicines.