Yuan Yihao, Li Jiapeng, Wei Guotao, Shen Ziyi, Li Bo, Wu Jiawei, Liu Jing
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science & Medicine, Northwest University, Xian 710069, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing 100190, China.
ACS Biomater Sci Eng. 2025 Jun 9;11(6):3145-3164. doi: 10.1021/acsbiomaterials.4c02029. Epub 2025 May 27.
The human antimicrobial peptide LL-37 exhibits broad antimicrobial efficacy. However, it has several limitations including high production costs, reduced efficacy under physiological conditions, susceptibility to proteolytic degradation and significant toxicity to human cells. Recent research has improved the clinical potential of peptide LL-37 through multiple systematic modifications. Therefore, we review the various modification techniques for LL-37 and explore the structure-activity relationships that underpin its antimicrobial properties. We also highlight the benefits of LL-37 derivatives and investigate their mechanisms of action against bacterial infections, particularly their effects on biofilms and cell membranes. Furthermore, we review the antimicrobial applications of LL-37 derivatives, examine nanocarrier systems for their delivery, and highlight the potential synergy between these derivatives and traditional antibiotics. Finally, it assesses the status of LL-37 derivatives in clinical applications, identifies ongoing challenges, and provides insights into future modifications and potential applications. This review aims to offer valuable strategies for enhancing LL-37 derivatives and facilitating their transition from laboratory research to clinical practice.
人类抗菌肽LL-37具有广泛的抗菌功效。然而，它存在一些局限性，包括生产成本高、在生理条件下功效降低、易受蛋白水解降解以及对人类细胞具有显著毒性。最近的研究通过多种系统修饰提高了肽LL-37的临床潜力。因此，我们综述了LL-37的各种修饰技术，并探讨了支撑其抗菌特性的构效关系。我们还强调了LL-37衍生物的益处，并研究了它们对抗细菌感染的作用机制，特别是它们对生物膜和细胞膜的影响。此外，我们综述了LL-37衍生物的抗菌应用，研究了用于其递送的纳米载体系统，并强调了这些衍生物与传统抗生素之间的潜在协同作用。最后，评估LL-37衍生物在临床应用中的现状，识别当前面临的挑战，并为未来的修饰和潜在应用提供见解。本综述旨在提供有价值的策略，以增强LL-37衍生物，并促进其从实验室研究向临床实践的转变。
