Simultaneously Antimicrobial, Protein-Repellent, and Cell-Compatible Polyzwitterion Networks: More Insight on Bioactivity and Physical Properties

A poly­(oxanorbornene)-based polyzwitterion with primary ammonium and carboxylate groups (PZI) 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 (PZI, the polycarboxybetaine (PCB), and the polysulfobetaine (PSB)) are compared to understand the molecular origins of this unusual bioactivity. Additionally, the three polyzwitterions and the antimicrobial polycationic SMAMP 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 PZI, yet reversible interaction with lysozyme is observed at pH 7 and 8. In the presence of bivalent cations, reversible fibrinogen adhesion is observed on PZI and PSB but not on PCB. This might explain why mammalian cells grow on PZI and PSB but not on PCB. PZI does not show human plasma adhesion, whereas PCB and PSB have 0.27 and 0.48 ng mm–2 adhered plasma and SMAMP even at 6.3 ng mm–2. Both PZI and SMAMP show strong serum adhesion, whereas no serum adhered to PCB and only a little adhered to PSB. 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 NR4+ groups are unaffected. Both PZI and PCB showed no or only a little bacterial adhesion. PCB is also intrinsically antimicrobial against E. coli and S. aureus bacteria and thus is also simultaneously protein-repellent and antimicrobially active. Thus, although the carboxylate groups of PZI and PCB seem to be a prerequisite for the dual antimicrobial activity and protein-repellency, the pH responsiveness of the primary ammonium group seems to make the PZI molecule vulnerable for protein adhesion in fluids that are slightly out of the physiological range