Abstract
Nanoparticles loaded with cancer epitope peptides have shown great potential for cancer immunotherapy. However, preparing small-sized nanoparticles with a narrow size distribution for the co-delivery of multiple antigen peptides has been a challenge. The lack of scalable and reproducible nanoparticle preparation methods has also hindered the widespread application of nanoparticles in cancer immunotherapy. In this study, we developed lymph node-targeted nanoparticles for the co-delivery of a group of sixteen pancreatic cancer antigen peptides and a STING agonist as an adjuvant using the flash nanocomplexation (FNC) method. The nanoparticles generated by FNC had a smaller particle size and a narrower size distribution compared to the nanoparticles prepared by bulk mixing. The FNC-generated nanoparticles enhanced human monocyte activation, demonstrated lymph node-targeting effect, and activated dendritic cells in vivo, all without any observable toxicity. Additionally, in vivo studies demonstrated the strong anti-tumor efficacy of these nanoparticles in an orthotopic pancreatic cancer mouse model. This nanoparticle platform enables the effective co-delivery of multiple antigen epitope peptides and an adjuvant to the lymph nodes. Furthermore, the scalability and reproducibility of the FNC method could facilitate the rapid clinical translation of this nanoparticle platform.