Su Yuanzhen, Xu Weiguo, Wei Qi, Ma Yang, Ding Jianxun, Chen Xuesi
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Sci Bull (Beijing). 2023 Feb 15;68(3):284-294. doi: 10.1016/j.scib.2023.01.024. Epub 2023 Jan 19.
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-K) and poly(L-phenylalanine)-block-poly(D-lysine) (P-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-K-OVA and P-K-OVA were easily prepared by mixing solutions of P-K or P-K and the model antigen chicken ovalbumin (OVA), respectively, with loading efficiencies of almost 100%. Compared to P-K-OVA, P-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-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.
生物活性分子的手性与其功能密切相关。普遍分布于细菌细胞壁中的D-氨基酸可引发强烈的抗感染免疫反应。受此启发，合成了两种手性多肽，聚（L-苯丙氨酸）-嵌段-聚（L-赖氨酸）（P-K）和聚（L-苯丙氨酸）-嵌段-聚（D-赖氨酸）（P-K），并将其用作纳米疫苗的纳米佐剂用于癌症预防和治疗。在磷酸盐缓冲盐水中超声辅助溶解过程中，两亲性多肽自组装成直径约30nm的纳米颗粒。纳米疫苗P-K-OVA和P-K-OVA分别通过将P-K或P-K与模型抗原鸡卵清蛋白（OVA）的溶液混合而轻松制备，负载效率几乎为100%。与P-K-OVA相比，P-K-OVA更强烈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-K-OVA与抗PD-1抗体联合使用时，肿瘤抑制率达到94.9%，甚至97.0%。因此，手性多肽纳米颗粒代表了用于各种纳米疫苗的简单、高效且广泛适用的纳米佐剂。
