State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Adv Sci (Weinh). 2022 May;9(14):e2105955. doi: 10.1002/advs.202105955. Epub 2022 Mar 13.
As a novel type of antibiotic alternative, peptide-based antibacterial drug shows potential application prospects attributable to their unique mechanism for lysing the membrane of pathogenic bacteria. However, peptide-based antibacterial drugs suffer from a series of problems, most notably their immature stability, which seriously hinders their application. In this study, self-assembling chimeric peptide nanoparticles (which offer excellent stability in the presence of proteases and salts) are constructed and applied to the treatment of bacterial infections. In vitro studies are used to demonstrate that peptide nanoparticles NPs1 and NPs2 offer broad-spectrum antibacterial activity and desirable biocompatibility, and they retain their antibacterial ability in physiological salt environments. Peptide nanoparticles NPs1 and NPs2 can resist degradation under high concentrations of proteases. In vivo studies illustrate that the toxicity caused by peptide nanoparticles NPs1 and NPs2 is negligible, and these nanoparticles can alleviate systemic bacterial infections in mice and piglets. The membrane permeation mechanism and interference with the cell cycle differ from that of antibiotics and mean that the nanoparticles are at a lower risk of inducing drug resistance. Collectively, these advances may accelerate the development of peptide-based antibacterial nanomaterials and can be applied to the construction of supramolecular nanomaterials.
作为一种新型的抗生素替代品，基于肽的抗菌药物由于其裂解病原菌膜的独特机制，显示出潜在的应用前景。然而，基于肽的抗菌药物存在一系列问题，最突出的是其不成熟的稳定性，这严重阻碍了它们的应用。在这项研究中，构建了自组装嵌合肽纳米粒子（在存在蛋白酶和盐的情况下具有优异的稳定性），并将其应用于细菌感染的治疗。体外研究表明，肽纳米粒子 NPs1 和 NPs2 具有广谱抗菌活性和良好的生物相容性，并且在生理盐环境中保持其抗菌能力。肽纳米粒子 NPs1 和 NPs2 可以在高浓度蛋白酶下抵抗降解。体内研究表明，肽纳米粒子 NPs1 和 NPs2 引起的毒性可以忽略不计，并且这些纳米粒子可以减轻小鼠和仔猪的全身细菌感染。其膜渗透机制和对细胞周期的干扰与抗生素不同，这意味着纳米粒子引发耐药性的风险较低。总的来说，这些进展可能会加速基于肽的抗菌纳米材料的发展，并可应用于超分子纳米材料的构建。
