Kurowska Monika, Eickenscheidt Alice, Al-Ahmad Ali, Lienkamp Karen
Bioactive Polymer Synthesis and Surface Engineering Group, Department of Microsystems Engineering (IMTEK) and Freiburg Centre for Interactive Materials and Bioinspired Technologies (FIT), Georges-Köhler-Allee 105, 79110 Freiburg, Germany.
Department of Operative Dentistry and Periodontology, Medical Centre of the University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
ACS Appl Bio Mater. 2018 Sep 17;1(3):613-626. doi: 10.1021/acsabm.8b00100. Epub 2018 Jul 27.
A poly(oxanorbornene)-based polyzwitterion with primary ammonium and carboxylate groups () has been reported previously as the first simultaneously antimicrobial and protein-repellent polyzwitterion. Here, additional physical and biological properties of three poly(oxanorbornene)-based polyzwitterions with different functional groups (, the polycarboxybetaine , and the polysulfobetaine ) are compared to understand the molecular origins of this unusual bioactivity. Additionally, the three polyzwitterions and the antimicrobial, polycationic are exposed to proteins, bacteria suspensions, human plasma and serum. These interactions are investigated by surface plasmon resonance spectroscopy. In protein adhesion studies, neither fibrinogen nor lysozyme adhere irreversibly to , yet reversible interaction with lysozyme is observed at pH 7 and 8. In the presence of bivalent cations, reversible fibrinogen adhesion on and is observed, but not on . This might explain why mammalian cells grow on and , but not on . does not show human plasma adhesion, while and have 0.27 and 0.48 ng mm adhered plasma, and even 6.3 ng mm. Both and show strong serum adhesion, while no serum adhered to , and only little to . This could be related to the pH difference between serum and plasma, to which the pH-responsive primary ammonium groups are susceptible, while the permanently charged NR groups are unaffected. Both and showed none or only little bacterial adhesion. is also intrinsically antimicrobial against . and . bacteria and thus is also simultaneously protein-repellent and antimicrobially active. Thus, while the carboxylate groups of and seems to be a prerequisite for the dual antimicrobial activity and protein-repellency, the pH-responsiveness of the primary ammonium group seems to make the molecule vulnerable for protein adhesion in fluids that are slightly out of the physiological range.
一种带有伯铵基和羧基的聚（氧杂降冰片烯）基两性离子聚合物（ ）此前已被报道为首个同时具有抗菌和抗蛋白质性能的两性离子聚合物。在此，对三种具有不同官能团的聚（氧杂降冰片烯）基两性离子聚合物（ 、聚羧基甜菜碱 和聚磺基甜菜碱 ）的其他物理和生物学性质进行了比较，以了解这种异常生物活性的分子起源。此外，将这三种两性离子聚合物以及抗菌性聚阳离子聚合物 暴露于蛋白质、细菌悬液、人血浆和血清中。通过表面等离子体共振光谱对这些相互作用进行了研究。在蛋白质黏附研究中，纤维蛋白原和溶菌酶都不会不可逆地黏附于 ，但在pH值为7和8时观察到与溶菌酶的可逆相互作用。在二价阳离子存在的情况下，观察到纤维蛋白原在 和 上的可逆黏附，但在 上未观察到。这可能解释了为什么哺乳动物细胞能在 和 上生长，而不能在 上生长。 未表现出与人血浆的黏附，而 和 分别有0.27 ng/mm²和0.48 ng/mm²的血浆黏附， 甚至有6.3 ng/mm²。 和 都表现出强烈的血清黏附，而 没有血清黏附， 仅有少量血清黏附。这可能与血清和血浆之间的pH差异有关，pH响应性的伯铵基对此敏感，而永久带电的NR 基团不受影响。 和 均未表现出或仅表现出少量细菌黏附。 对 、 和 细菌也具有内在抗菌性，因此也同时具有抗蛋白质和抗菌活性。因此，虽然 和 的羧基似乎是双重抗菌活性和抗蛋白质性能的先决条件，但伯铵基的pH响应性似乎使 分子在略超出生理范围的流体中易发生蛋白质黏附。
