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 dis-tributed 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) (PL-K) and poly(L- phenylalanine)-block-poly(D-lysine) (PD-K), were synthesized and used as nanoadjuvants of nanovacci-nes 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 PL-K-OVA and PD-K-OVA were easily prepared by mixing solutions of PL-K or PD-K and the model antigen chicken ovalbumin (OVA), respectively, with loading efficiencies of almost 100%. Compared to PL-K-OVA, PD-K-OVA more robustly induced dendritic cell maturation, antigen cross-presentation, and adaptive immune response. More importantly, it effectively prevented and trea-ted the OVA-expressed B16-OVA melanoma model. PD-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.(c) 2023 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.

Automated summary

Two types of chiral polypeptide nanoparticles were used as nanoadjuvants for cancer prevention and therapy, exhibiting excellent performance in inducing immune response and anti-tumor effects.