Recent Advances in Nanomodulators for Augmenting Cancer Immunotherapy in Cold Tumors: Insights from Drug Delivery to Drug-Free Strategies

Abstract

Immunotherapy has significantly improved cancer treatment, yet the immunosuppressive tumor microenvironment (TME) remains a substantial impediment to therapeutic efficacy. Nanomodulators have emerged as promising tools to address immunosuppressive factors within the TME, enhancing clinical interventions such as immunotherapy, chemotherapy, and radiotherapy while minimizing associated safety risks with immune modulators. In this review, recent advancements are spotlighted in TME-targeted nanomodulators from drug delivery to drug-free concepts. First, nanomodulators designed to synergize with various immunomodulatory agents, including gene tools (mRNA, siRNA, miRNA, plasmid DNA, and CRISPER system), cytokines, immune agonists, and inhibitors are analyzed. Subsequently, recently developed drug-free nanomodulators designed to modulate the physicochemical and biological properties in the microenvironment of solid tumors are succinctly presented. Finally, integrative perspectives on the future development and challenges of nanomodulators in assisting cancer immunotherapy are offered as conclusions.