pH-Responsive Charge Convertible Hyperbranched Poly(ionic liquid) Nanoassembly with High Biocompatibility for Resistance-Free Antimicrobial Applications.

ABSTRACT

As a potential alternative to antibiotics, hyperbranched poly(ionic liquid)s (HPILs) have demonstrated significant potential in combating bacterial biofilms. However, their high cation density poses a high risk of toxicity, greatly limiting their in vivo applications. In this study, we constructed a biocompatible HPIL (HPIL-Glu) from a hyperbranched polyurea core with modified terminals featuring charge-convertible ionic liquids. These ionic liquid moieties consist of an ammonium-based cation and a gluconate (Glu) organic counter. HPIL-Glu could form a homogeneous nanoassembly in water and exhibited a pH-responsive charge conversion property. Under neutral conditions, Glu shielded the positively charged surface, minimizing the toxicity. In a mildly acidic environment, Glu protonation exposes cationic moieties to biofilm eradication. Comprehensive antimicrobial assessments demonstrate that HPIL-Glu effectively kills bacteria and promotes the healing of bacteria-infected chronic wounds. Furthermore, prolonged exposure to HPIL-Glu does not induce antimicrobial resistance.