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祝贺冯文丽的文章在ACS Nano接受发表!

发布人:管理员发布时间:2024-03-14

冯文丽在ACS Nano发表题为“Poly(d-amino acid) Nanoparticles Target Staphylococcal Growth and Biofilm Disassembly by Interfering with Peptidoglycan Synthesis”的文章。本文提出了D-氨基酸是生物膜分解的信号。然而,意想不到的代谢途径严重削弱了D-氨基酸在生物膜分解中的利用,导致效率不理想。本文构建了具有阻断细胞内代谢能力的三维聚(D-氨基酸)纳米颗粒(NPs),目的是分解生物膜。所得的聚(α-N-丙烯酰基-d-苯丙氨酸)-嵌段-聚(β-N-丙烯酰基-D-氨基丙氨酸NPs(表示为FA NPs)表面存在D-氨基丙氨酸的α-氨基和α-羧基,保证了FA NPs可以通过PG结合蛋白4(PBP4)的介导有效地插入细菌肽聚糖(PG)中。随后,FA NPs触发与PG相连的淀粉样纤维的分离,并减少细胞外聚合物物质(EPS)中多糖和蛋白质的数量。最后,FA NPs破坏了EPS的结构稳定性,导致生物膜的分解。基于这一特征,FA NPs通过促进Sita在生物膜内的渗透,显著增强了包封的西他沙星倍半水合物(Sita)的杀伤力,实现了对小鼠葡萄球菌生物膜的完全消除。因此,本研究有力地证明了FA NPs可以有效提高生物膜拆解效果,为细菌生物膜感染的治疗提供巨大潜力。

Abstract: D-Amino acids are signals for biofilm disassembly. However, unexpected metabolic pathways severely attenuate the utilization of d-amino acids in biofilm disassembly, resulting in unsatisfactory efficiency. Herein, three-dimensional poly(d-amino acid) nanoparticles (NPs), which possess the ability to block intracellular metabolism, are constructed with the aim of disassembling the biofilms. The obtained poly(α-N-acryloyl-D-phenylalanine)-block-poly(β-N-acryloyl-D-aminoalanine NPs (denoted as FA NPs) present α-amino groups and α-carboxyl groups of D-aminoalanine on their surface, which guarantees that FA NPs can effectively insert into bacterial peptidoglycan (PG) via the mediation of PG binding protein 4 (PBP4). Subsequently, the FA NPs trigger the detachment of amyloid-like fibers that connect to the PG and reduce the number of polysaccharides and proteins in extracellular polymeric substances (EPS). Finally, FA NPs damage the structural stability of EPS and lead to the disassembly of the biofilm. Based on this feature, FA NPs significantly enhance the killing efficacy of encapsulated sitafloxacin sesquihydrate (Sita) by facilitating the penetration of Sita within the biofilm, achieving complete elimination of Staphylococcal biofilm in mice. Therefore, this study strongly demonstrates that FA NPs can effectively improve biofilm disassembly efficacy and provide great potential for bacterial biofilm infection treatment.