Giri Anupama, Aquib Md, Choudhury Anmol, Kannaujiya Vinod Kumar, Lim Jie Lay, Gu Zi, Lenardon Megan D, Boyer Cyrille
Cluster for Advanced Macromolecular Design (CAMD) and School of Chemical Engineering, UNSW, Sydney, New South Wales, Australia.
School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, New South Wales, Australia.
Macromol Rapid Commun. 2025 Sep;46(17):e00224. doi: 10.1002/marc.202500224. Epub 2025 Jun 17.
The rise of multidrug-resistant (MDR) pathogens poses a critical threat to global health, exacerbated by the overuse of antibiotics and the lack of effective alternatives. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their broad-spectrum activity and unique mechanisms of action. However, several challenges such as enzymatic degradation, high production costs, and potential cytotoxicity have hindered their clinical translation. To overcome these limitations, antimicrobial polymers (APs) inspired by AMPs have been developed using controlled/living polymerization techniques. In this study, a series of degradable, disulfide-containing antimicrobial polymers incorporating benzyl lipoate, a lipoic acid (LA) derivative, is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Benzyl lipoate is prepared by modification of LA with benzyl alcohol to introduce a hydrophobic moiety and copolymerized with a primary amine-containing cationic monomer and hydrophilic co-monomers, including hydroxyethyl acrylamide (HEAm) and poly(ethylene glycol) methyl ether acrylate (PEGMEA). The resulting polymers demonstrated antimicrobial activity against drug-resistant Pseudomonas aeruginosa, improved hemocompatibility, and redox-responsive degradability. This study highlights the potential of disulfide-based APs as a next-generation strategy for combating MDR infections while ensuring controlled degradability.
多重耐药（MDR）病原体的出现对全球健康构成了严重威胁，抗生素的过度使用和缺乏有效的替代药物使这一威胁更加严峻。抗菌肽（AMPs）因其广谱活性和独特的作用机制而成为有前景的候选药物。然而，诸如酶降解、高生产成本和潜在的细胞毒性等挑战阻碍了它们的临床应用。为了克服这些限制，受AMPs启发的抗菌聚合物（APs）已通过可控/活性聚合技术得以开发。在本研究中，通过可逆加成-断裂链转移（RAFT）聚合反应合成了一系列含有苄基硫辛酸酯（一种硫辛酸（LA）衍生物）的可降解、含二硫键的抗菌聚合物。苄基硫辛酸酯是通过用苄醇对LA进行修饰以引入疏水部分而制备的，并与含伯胺的阳离子单体和亲水性共聚单体（包括羟乙基丙烯酰胺（HEAm）和聚（乙二醇）甲基醚丙烯酸酯（PEGMEA））共聚。所得聚合物对耐药铜绿假单胞菌表现出抗菌活性，改善了血液相容性，并具有氧化还原响应性降解能力。这项研究突出了基于二硫键的APs作为对抗MDR感染的下一代策略同时确保可控降解性的潜力。
