The increasing prevalence of microbial resistance requires new antibacterial concepts for selective targeting and killing of pathogenic bacteria. Here, we report the synthesis of a heteromultivalent nanogel system against Pseudomonas aeruginosa (P. aeruginosa). These nanogels are based on biocompatible polyglycerols and functionalized with sugar ligands fucose (Fuc) or galactose (Gal) for P. aeruginosa targeting. With a further modification of these nanogels with BMAP-18 short chain peptides (GRFKRFRKKFKKLFKKLS), we have achieved > 99.99% inactivation of planktonic and > 99.9% inactivation of biofilm-coated P. aeruginosa within 12 h of treatment. Additionally, the system demonstrates broad-spectrum antimicrobial potential, effectively inhibiting Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA). This modular design offers a promising strategy for the development of next-generation antimicrobial therapies targeting biofilm-associated infections and MDR bacteria.
