Lin Liming, Chi Jiaying, Yan Yilang, Luo Rui, Feng Xiaoqian, Zheng Yuwei, Xian Dongyi, Li Xin, Quan Guilan, Liu Daojun, Wu Chuanbin, Lu Chao, Pan Xin
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
College of Pharmacy, Jinan University, Guangzhou 511443, China.
Acta Pharm Sin B. 2021 Sep;11(9):2609-2644. doi: 10.1016/j.apsb.2021.07.014. Epub 2021 Jul 21.
Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.
膜破坏肽/肽模拟物(MDPs)是一类抗菌或抗癌物质,与传统化疗药物作用于DNA或特定酶等精确靶点不同,它们通过物理破坏细胞膜呈现出一种通用的杀伤机制。由于其作用迅速、具有广谱活性以及潜在阻碍耐药性产生的作用机制,MDPs在耐药时代越来越被视为未来的治疗药物。最近,越来越多的实验证据表明,MDPs还可以用作佐剂来增强其他药物的治疗效果。在本综述中,我们评估了有关MDPs广谱抗菌特性和抗癌活性的文献,并总结了MDPs单独使用或与其他药物联合使用的当前进展及作用机制。值得注意的是,本综述重点介绍了各种基于MDP的药物递送系统设计方面的最新进展,这些进展可以提高MDPs的治疗效果、将副作用降至最低,并促进多种化疗药物的共同递送,以实现更有效的抗菌和抗癌治疗。