A Red Blood Cell-Hitchhiking Dendrimer Nanovaccine Potentiates Antitumor Immunity via Lymphoid Organ Targeting

Abstract

Efficient antigen delivery to antigen-presenting cells remains a critical challenge in cancer nanovaccine development. In this study, we develop a dendrimer-based nanovaccine (DenV) for efficient tumor treatment and prevention via a red blood cell (RBC) hitchhiking strategy. Utilizing phenylboronic acid-grafted dendrimers, model antigen ovalbumin (OVA) and immune adjuvant CpG oligodeoxynucleotide (CpG ODN) can be efficiently co-loaded to get DenV with a relatively simple fabrication process. Upon further RBC anchoring, DenV@RBC demonstrates a distinct application feature from DenV with a desired delivery profile to lymphoid organs. In vivo antitumor results in a mouse subcutaneous melanoma model show that both DenV and DenV@RBC achieve excellent antitumor effects following systemic administration, where the therapeutic efficacy of DenV@RBC is slightly superior to that of DenV. Meanwhile, DenV and DenV@RBC allow excellent tumor-preventive effects, regardless of local or systematic administration routes. It is also found that DenV is more robust upon local injection, while DenV@RBC yields better tumor prevention performance when administered systemically via the bloodstream. Our study offers a dendrimer-based strategy with interaction to natural RBCs for the development of highly efficient nanovaccines and holds substantial application potential in the field of cancer immunotherapy.