Targeting chiral carbon dots to enhance melanoma immunotherapy

Nanovaccines possess tremendous potential in efficient antigen delivery and the induction of robust tumor-specific immune responses. Nevertheless, the development of nanovaccines with enhanced efficacy and improved safety is an ongoing quest. In this research, chiral carbon dots (L/D-CDs) were modified with lactobionic acid (LA) to fabricate LLA/DLA. Subsequently, L/D-CDs and LLA/DLA were combined with the model antigen ovalbumin (OVA) to formulate nanovaccines (L-OVA, D-OVA, LLAO, and DLAO). Interestingly, D-type nanovaccines (D-OVA and DLAO) exhibited higher antigen uptake by dendritic cells (DCs) and more potent immune activities in contrast to their corresponding L-type nanovaccines (L-OVA and LLAO), suggesting a chiral-dependent augmentation in antigen presentation and immunogenicity. Moreover, LA-modified nanovaccines (LLAO and DLAO) showed enhanced antigen processing and presentation, along with markedly elevated expression of CD80 and CD86. Immunization with DLAO in tumor-bearing mice induced the most significant antigen-specific T cell proliferation in the spleen, lymph nodes (LNs), and tumor sites, which further translated into the most remarkable therapeutic effects. Taken together, these results underscore the considerable promise of leveraging chirality and targeting to potentiate anti-tumor immunity.