Université de Picardie Jules Verne, AGIR: Agents Infectieux, Résistance et Chimiothérapie, Amiens, France.
Med Res Rev. 2019 Nov;39(6):2343-2396. doi: 10.1002/med.21588. Epub 2019 Apr 19.
Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti-infective agents, very few new classes of antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti-infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called "Trojan horse" strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell-penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse-inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug-resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.
抗菌药物耐药性已成为有效治疗感染性疾病的巨大挑战。除了少数新型抗感染药物外，很少有新类别的抗生素被成功开发用于治疗。尽管众多科学家进行了研究，但对抗抗菌药物（ATB）耐药性的斗争一直是一项长期持续的努力，因为病原体通过各种策略迅速适应和进化，以逃避 ATB 的作用。在抗生素耐药的其他机制中，微生物周围复杂的包膜尤其成为几乎所有抗感染药物的主要障碍。此外，哺乳动物细胞膜也成为针对细胞内病原体的 ATB 的另一个障碍。为了克服这些生物膜，科学家们开发了药物传递系统来帮助药物穿越细胞壁；这些被称为“特洛伊木马”策略。在这些递送系统中，ATB 分子可以与许多不同类型的载体之一结合。这些载体可以包括以下任何一种：铁载体、抗菌肽、细胞穿透肽、抗体，甚至是纳米颗粒。近年来，越来越多的研究报告表明，受“特洛伊木马”启发的递送系统是一种有效的策略，可以扩大治疗方案的武器库，和/或增强传统 ATB 对耐药微生物的有效性，同时还可以最小化这些药物的副作用。在本文中，我们旨在回顾和报告在当前 ATB 耐药性不断增加的背景下，这些新出现的 ATB 递药策略的最新进展。
