Trimethyl chitosan-hyaluronic acid nanoparticle-loaded hydrogel potentiates dendritic cell-based immunotherapy against breast cancer.

BACKGROUND: Cancer immunotherapy has shown considerable promise, particularly through dendritic cell (DC)-based vaccines, which are capable of inducing potent, durable, and tumor-specific immune responses. However, their clinical efficacy remains limited by the immature phenotype of DCs, inefficient antigen presentation, and the immunosuppressive tumor microenvironment.

METHODS AND RESULTS: In the present study, we developed a novel delivery platform composed of trimethyl chitosan-hyaluronic acid nanoparticles (TMC-HA NPs) loaded with tumor cell lysate (TCL) and subsequently encapsulated within an alginate hydrogel (TCL/NPs-Gel). This nanocomposite system was designed to enhance dendritic cell activation and promote robust antitumor immune responses. In vitro, TCL/NPs-Gel significantly increased CD86 expression on bone marrow-derived dendritic cells (BMDCs) compared with TCL/NPs and the negative control, indicating enhanced activation of BMDCs. Furthermore, in a murine breast cancer model (BALB/c mice), subcutaneous administration of TCL/NPs-Gel combined with immature BMDCs significantly reduced tumor growth compared with the Control and TCL/NPs-Gel groups, increased the frequency of CD11c+CD80+ splenic DCs and CD11c+CD86+ splenic DCs (relative to the Control group), and improved histopathological features, including reduced mitotic activity and increased tumor-infiltrating lymphocytes, compared with the Control group.

CONCLUSIONS: Collectively, our findings suggest that co-administration of immature BMDCs with a TCL-loaded TMC-HA nanoparticle-encapsulated alginate hydrogel represents a promising strategy for enhancing the therapeutic efficacy of dendritic cell-based cancer vaccines against breast cancer.