Chiral polypeptide nanoparticles as nanoadjuvants of nanovaccines for efficient cancer prevention and therapy

The chirality of bioactive molecules is closely related to their functions. D-amino acids commonly distributed in the bacterial cell walls trigger a robust anti-infective immune response. Inspired by that, two kinds of chiral polypeptides, poly(L-phenylalanine)-block-poly(L-lysine) (P_L-K) and poly(L-phenylalanine)-block-poly(D-lysine) (P_D-K), were synthesized and used as nanoadjuvants of nanovaccines for cancer prevention and therapy. The amphiphilic polypeptides self-assembled into nanoparticles with a diameter of about 30 nm during ultrasonic-assisted dissolution in phosphate-buffered saline. The nanovaccines P_L-K-OVA and P_D-K-OVA were easily prepared by mixing solutions of P_L-K or P_D-K and the model antigen chicken ovalbumin (OVA), respectively, with loading efficiencies of almost 100%. Compared to P_L-K-OVA, P_D-K-OVA more robustly induced dendritic cell maturation, antigen cross-presentation, and adaptive immune response. More importantly, it effectively prevented and treated the OVA-expressed B16-OVA melanoma model. P_D-K-OVA achieved a tumor inhibition rate of 94.9% and even 97.0% by combining with anti-PD-1 antibody. Therefore, the chiral polypeptide nanoparticles represent simple, efficient, and extensively applicable nanoadjuvants for various nanovaccines.