Emerging Strategies for Local Delivery of Immune Checkpoint Inhibitors to Potentiate Cancer Immunotherapy: Current Status and Future Prospects

Cancer constitutes a significant threat to patients' lives worldwide. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) that boost antitumor immunity by targeting immune checkpoint components, has emerged as a promising strategy for its treatment in recent years. However, the objective response rates of the ICIs are unsatisfactory. As the primary route, systemic administration of ICIs is often accompanied by immune-related adverse events. Local delivery of ICIs serves as a potential therapeutic strategy that can improve the efficacy while simultaneously reducing side effects through precise drug release at the tumor site. Initial validation of direct local application of ICIs for tumors in clinical trials has indicated reduced side effects and improved efficacy, while low bioavailability remains a challenge. Furthermore, research on various carriers, including nanoparticles, microneedles, hydrogels, combined platforms, and implantable devices for local release of ICIs has exhibited applying potential in treating murine tumors, among which combined platforms such as combined hydrogel system hold the highest promise due to their encompassment of the advantages of multiple carriers. These carriers, by incorporating ICIs and other therapeutics, could manage cancers more potently, which needs to be confirmed in clinical trials after the refinement of their biocompatibility. This review summarizes the latest research advancements regarding local administration of ICIs, with a particular focus on the carriers for local delivery as well as the combination therapies, thus providing novel insights and research guidance for scholars to enhance the efficacy of locally delivered ICIs on managing multiple cancers in the future.