Alfei Silvana, Schito Anna Maria
Department of Pharmacy (DiFAR), University of Genoa, Viale Cembrano 4, I-16148 Genova, Italy.
Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, I-16132 Genova, Italy.
Nanomaterials (Basel). 2020 Oct 14;10(10):2022. doi: 10.3390/nano10102022.
The alarming increase in antimicrobial resistance, based on the built-in abilities of bacteria to nullify the activity of current antibiotics, leaves a growing number of bacterial infections untreatable. An appealing approach, advanced in recent decades, concerns the development of novel agents able to interact with the external layers of bacteria, causing irreparable damage. Regarding this, some natural cationic antimicrobial peptides (CAMPs) have been reconsidered, and synthetic cationic polymers, mimicking CAMPs and able to kill bacteria by non-specific detrimental interaction with the negative bacterial membranes, have been proposed as promising solutions. Lately, also dendrimers were considered suitable macromolecules for the preparation of more advanced cationic biomimetic nanoparticles, able to harmonize the typical properties of dendrimers, including nanosize, mono-dispersion, long-term stability, high functionality, and the non-specific mechanism of action of CAMPs. Although cationic dendrimers are extensively applied in nanomedicine for drug or gene delivery, their application as antimicrobial agents is still in its infancy. The state of the art of their potential applications in this important field has therefore been reviewed here, with particular attention to the innovative case studies in the literature including also amino acid-modified polyester-based dendrimers, practically unexplored as membrane-active antimicrobials and able to kill bacteria on contact.
基于细菌消除当前抗生素活性的内在能力,抗菌药物耐药性惊人地增加,导致越来越多的细菌感染无法治疗。近几十年来提出的一种有吸引力的方法是开发能够与细菌外层相互作用并造成不可修复损伤的新型药物。关于这一点,一些天然阳离子抗菌肽(CAMP)已被重新审视,并且有人提出模仿CAMP并通过与细菌负电荷膜的非特异性有害相互作用杀死细菌的合成阳离子聚合物是有前景的解决方案。最近,树枝状大分子也被认为是制备更先进的阳离子仿生纳米颗粒的合适大分子,能够兼具树枝状大分子的典型特性,包括纳米尺寸、单分散性、长期稳定性、高功能性以及CAMP的非特异性作用机制。尽管阳离子树枝状大分子在纳米医学中广泛应用于药物或基因递送,但其作为抗菌剂的应用仍处于起步阶段。因此,本文综述了它们在这一重要领域潜在应用的现状,特别关注文献中的创新案例研究,包括氨基酸修饰的聚酯基树枝状大分子,它们作为膜活性抗菌剂几乎未被探索,但能够在接触时杀死细菌。