State Key Laboratory of Medicinal Chemical Biology; Key Laboratory of Functional Polymer Materials, Ministry of Education; and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P.R. China.
University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands.
Sci Adv. 2020 Aug 14;6(33):eabb1112. doi: 10.1126/sciadv.abb1112. eCollection 2020 Aug.
Extracellular polymeric substances (EPS) hold infectious biofilms together and limit antimicrobial penetration and clinical infection control. Here, we present zwitterionic micelles as a previously unexplored, synthetic self-targeting dispersant. First, a pH-responsive poly(ε-caprolactone)--poly(quaternary-amino-ester) was synthesized and self-assembled with poly(ethylene glycol)--poly(ε-caprolactone) to form zwitterionic, mixed-shell polymeric micelles (ZW-MSPMs). In the acidic environment of staphylococcal biofilms, ZW-MSPMs became positively charged because of conversion of the zwitterionic poly(quaternary-amino-ester) to a cationic lactone ring. This allowed ZW-MSPMs to self-target, penetrate, and accumulate in staphylococcal biofilms in vitro. In vivo biofilm targeting by ZW-MSPMs was confirmed for staphylococcal biofilms grown underneath an implanted abdominal imaging window through direct imaging in living mice. ZW-MSPMs interacted strongly with important EPS components such as eDNA and protein to disperse biofilm and enhance ciprofloxacin efficacy toward remaining biofilm, both in vitro and in vivo. Zwitterionic micellar dispersants may aid infection control and enhance efficacy of existing antibiotics against remaining biofilm.
细胞外聚合物质（EPS）将传染性生物膜结合在一起，并限制抗菌药物的渗透和临床感染控制。在这里，我们提出两性离子胶束作为一种以前未被探索的合成自靶向分散剂。首先，合成了一种 pH 响应性聚（己内酯）-聚（季铵酯），并与聚（乙二醇）-聚（己内酯）自组装形成两性离子混合壳聚合物胶束（ZW-MSPMs）。在葡萄球菌生物膜的酸性环境中，由于两性离子聚（季铵酯）转化为阳离子内酯环，ZW-MSPMs 带正电荷。这使得 ZW-MSPMs 能够在体外自我靶向、穿透和积累葡萄球菌生物膜。通过对活体小鼠进行直接成像，证实了 ZW-MSPMs 在植入式腹部成像窗口下生长的葡萄球菌生物膜中的体内生物膜靶向作用。ZW-MSPMs 与重要的 EPS 成分（如 eDNA 和蛋白质）强烈相互作用，以分散生物膜并增强环丙沙星对剩余生物膜的功效，无论是在体外还是体内。两性离子胶束分散剂可能有助于感染控制，并增强现有抗生素对剩余生物膜的疗效。
