Antigen-Loaded and Calcium-Incorporated Chitosan Oligosaccharide Nanoparticles for Dendritic Cell Cross-Presentation and Immunotherapy

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Background: Cancer vaccines, a type of immunotherapy for cancer treatment, have been extensively studied over the years. Antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages play a crucial role in vaccine therapies by presenting specific antigens to helper or cytotoxic T cells. Nanoparticles, which can extend the half-life of antigens and offer targeted delivery, are ideal vaccine delivery systems. Methods: In this study, we utilized calcium-incorporated chitosan oligosaccharide nanoparticles (Ca-CS NPs) as carriers to load ovalbumin (OVA) and deliver it to DCs. We characterized the NPs, examined the cell uptake, cross-presentation and immune responses by cell in vitro. In vivo, the biodistribution, immune response, anti-tumor effects and safety of NPs were examined. Results: Both CS-OVA NPs and Ca-CS-OVA NPs remained stable at 4 °C for 7 days and exhibited no cytotoxicity toward DC2.4 and RAW 264.7 cells. Compared with OVA and CS-OVA NPs, Ca-CS-OVA NPs effectively promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and induced stronger Th1 response in vitro. In vivo studies demonstrated that Ca-CS-OVA was distributed into lymph nodes and enhanced immune responses following subcutaneous administration. Moreover, Ca-CS-OVA NPs in combination with aCTLA-4 showed the best anti-tumor efficacy without adverse events. Conclusion: These findings indicate that Ca-CS NPs possess good biocompatibility and are a potential platform for cancer vaccine-based immunotherapies.

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