The chirality of bioactive molecules is closely related to their functions. D-amino acids commonly distributed in 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 for 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), 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 responses. More importantly, it effectively prevented and treated the OVA-expressing B16-OVA melanoma model. P_D-K-OVA achieved a tumor inhibition rate of 94.9% and even 97.0% by combining anti-PD-1 antibody. Therefore, chiral polypeptide nanoparticles represent simple, efficient, and extensively applicable nanoadjuvants for various nanovaccines.

生物活性分子的手性与其功能密切相关。通常分布在细菌细胞壁中的D型氨基酸会触发强大的抗感染免疫反应。受此启发，得到两种手性多肽，聚( L-苯丙氨酸)-嵌段-聚( L-赖氨酸)(P _L -K)和聚( L-苯丙氨酸)-嵌段-聚( D-赖氨酸)(P _D-K), 被合成并用作纳米疫苗的纳米佐剂，用于癌症的预防和治疗。在磷酸盐缓冲盐水中的超声辅助溶解过程中，两亲性多肽自组装成直径约 30 nm 的纳米颗粒。纳米疫苗 P _L -K-OVA 和 P _{D -K-OVA 很容易通过 P L} -K 或 P _D -K 与模型抗原鸡卵清蛋白 (OVA)的混合溶液制备，装载效率几乎为 100%。与 P _L -K-OVA 相比，P _D -K-OVA 更有效地诱导树突状细胞成熟、抗原交叉呈递和适应性免疫反应。更重要的是，它有效地预防和治疗了表达OVA的B16-OVA黑色素瘤模型。P_D -K-OVA结合抗PD-1抗体达到了94.9%甚至97.0%的抑瘤率。因此，手性多肽纳米粒子代表了用于各种纳米疫苗的简单、有效和广泛适用的纳米佐剂。