School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Singapore.
Macromol Rapid Commun. 2022 May;43(10):e2100812. doi: 10.1002/marc.202100812. Epub 2022 Apr 21.
Cationic polymers are under intense research to achieve prominent antimicrobial activity. However, the cellular and in vivo toxicity caused by nonspecific electrostatic interaction has become a major challenge for their practical applications. Here, the development of a "caging" strategy based on the use of a block copolymer consisting of a stealth block and an anionic block that undergoes degradation in presence of enzymes secreted by selective bacterial pathogens of interest is reported. The results have shown that antimicrobial cationic polymer brushes-coated gold nanorods (AuNRs) can be caged by the block polymer of poly(ethylene glycol) and anionic, lipase-degradable block of ε-caprolactone and methacrylic acid copolymer to afford neutrally charged surfaces. The caged AuNRs are activated by lipase released by bacteria of interest to endow an excellent bactericidal effect but show minimal binding and toxicity against mammalian cells and nonspecific bacteria that do not produce lipase. In this design, AuNRs play multifunctional roles as the scaffolds for polymer brushes, photothermal transducers, and imaging probes for traceable delivery of the activation and delivery of bactericidal cationic polymer brushes. The caging strategy opens new opportunities for the safe delivery of antimicrobial materials for the treatment of bacterial infections.
阳离子聚合物在实现显著抗菌活性方面受到了广泛关注。然而,非特异性静电相互作用引起的细胞毒性和体内毒性已成为其实际应用的主要挑战。在这里,报道了一种基于使用由嵌段共聚物组成的“笼状”策略的发展,该嵌段共聚物由具有隐身嵌段和在感兴趣的选择性细菌病原体分泌的酶存在下发生降解的阴离子嵌段组成。结果表明,抗菌阳离子聚合物刷涂覆的金纳米棒(AuNRs)可以被聚(乙二醇)和阴离子、脂肪酶可降解的ε-己内酯和甲基丙烯酸共聚物的嵌段聚合物“笼状”,以提供中性表面。被笼状的 AuNRs 被感兴趣的细菌释放的脂肪酶激活,赋予优异的杀菌效果,但对不产生脂肪酶的哺乳动物细胞和非特异性细菌的结合和毒性最小。在该设计中,AuNRs 发挥了多种功能,作为聚合物刷的支架、光热换能器和用于可追踪递送至杀菌阳离子聚合物刷的递药的成像探针。这种笼状策略为抗菌材料的安全输送提供了新的机会,可用于治疗细菌感染。