A chemically engineered water-soluble block copolymer for redox responsive SO₂ release in antibacterial therapy

Sulfur dioxide (SO₂) has emerged as a promising gasotransmitter for various therapeutic applications, including antibacterial activities. However, the potential of polymeric SO₂ donors for antimicrobial activities remains largely unexplored. Herein, we report a water-soluble, redox-responsive, SO₂-releasing amphiphilic block copolymer poly(polyethylene glycol methyl ether methacrylate) (PPEGMA)-b-poly(2-((2,4-dinitrophenyl)sulfonamido)ethyl methacrylate (PM)) (BCPx) to investigate their antibacterial properties. BCPx contains hydrophilic polyethylene glycol (PEG) pendants and a hydrophobic SO₂-releasing PM block, facilitating the formation of self-assembled nanoparticles (BCPxNp) in an aqueous medium, studied by critical aggregation concentration (CAC) measurements, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). BCPxNp exhibits sustained SO₂ release up to 12 h in the presence of glutathione (GSH), with a yield of 30-80% of theoretical SO₂ release. In vitro antibacterial studies unveil the outstanding antibacterial activity of BCP3Np against Gram-positive bacteria Bacillus subtilis, as evidenced by FESEM and live/dead cell fluorescence assay. We further elucidate the antibacterial mechanism through reactive oxygen species (ROS) generation studies. Overall, the polymer exhibits excellent biocompatibility at effective antimicrobial concentrations and provides insights into the design of a new class of SO₂-releasing polymeric antibacterial agents.