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

Abstract

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.

Stimulus‐Responsive Polyelectrolyte Surfaces: Switching Surface Properties from Polycationic/Antimicrobial to Polyzwitterionic/Protein‐Repellent

“…This is in good agreement with the data presented in the literature for the surface-attached poly(carboxybetaine) PCB (Figure 1), which had an IEP at 5.4 and a max of 50 mV. [9] At physiological pH, the zeta-potential phys of the network surface was slightly negative, which is also in agreement with literature data ( phys of PCB = −28 mV). The pK of the carboxylic acid group of PNCB-co-BP (determined as previously reported by Kurowska et al [9] ) was 4.1.…”

“…This should overcome the limited stability from which these materials previously reported by us suffer. [8,9,17] The target structures were polymers with PNCB repeat units (Figure 1). Three polymers were synthesized: the homopolymer (PNCB-Homo) and two copolymers consisting of PNCB repeat units as the major component, and a minor component that carried UV active cross-linker groups.…”

“…Structures of PNCB and other antimicrobial polyzwitterions described in the literature. PZI, [8] IA-PZI, [17] and PCB [9,18] are intrinsically antimicrobial when protonated. PSB [8,18] (used as a reference in this study) is protein-repellent but not active against bacteria.…”

Surface-Attached Poly(oxanorbornene) Hydrogels with Antimicrobial and Protein-Repellent Moieties: The Quest for Simultaneous Dual Activity

“…Only very recently, we were able to combine antimicrobial activity and protein-repellency in a single polymer component using a polyzwitterionic material [ 25 , 47 ]. While the exact mechanism of activity and the long term performance of this material are still being investigated, it seems that such a single component material might be an easier pathway to dual antimicrobial activity and protein repellency than finding the ‘sweet spot’ of the perfect balance of cationic and protein-repellent components in bifunctional polymer surfaces.…”

Surface Modification by Polyzwitterions of the Sulfabetaine-Type, and Their Resistance to Biofouling

“…Compared to the mostly employed anti-fouling materials based on poly(ethylene oxide), polyzwitterions excel for instance in their chemical stability, in particular against oxygen and other oxidants such as chlorine [14,15,16]. Although a large variety of zwitterionic moieties has been incorporated into polymers, the vast majority of studies have focused hitherto on three poly-zwitterion families, namely poly(phosphatidylcholine)s [10,17,18,19,20], poly(carboxybetaine)s [21,22,23,24,25,26,27,28,29], and poly(sulfobetaine)s [30,31,32,33,34,35,36,37,38,39]. While the interest in the former family is due to their similarity to phospholipids [40,41,42], the latter two families are characterized by good stability, high structural variability, and straightforward synthetic accessibility [2,3].…”