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.