Abstract
Excessive antibiotic usage has resulted in antibiotic resistance. This work introduces a novel ROS-responsive, cinnamaldehyde (CA)-based sulfonated all-polyester prodrug (RCSAP) to combat antibiotic resistance. RCSAP is a unique amphiphilic pseudo triblock copolymer comprising of two hydrophilic, heparin-mimicking sulfonated polyester (HSP) blocks and a hydrophobic polymeric block containing ROS-responsive CA thioacetal. RCSAP nanoparticles (NPs) not only achieve self-amplifying degradation and release, but orchestrate a “dual wielding” synergistic antibacterial mechanism. HSP shell competes with bacteria for host cell surface binding, hindering its internalization and infection. Simultaneously, ROS-responsive core liberates CA, boosting bacterial membrane permeability. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined. RCSAP NPs display exceptional antibacterial efficacy against both E. coli and S. aureus, as confirmed by survival analysis, colony-forming unit (CFU) quantification, microbial growth curve analysis, and live/dead bacterial viability assays. Importantly, RCSAP NPs effectively eradicated methicillin-resistant Staphylococcus aureus (MRSA). In addition, RCSAP NPs possess the unique ability to bind to S. aureus, aggregate and precipitate it. They competitively hinder S. aureus infection in both ARPE-19 and 293 T cells. Molecular simulation further verified the electrostatic interactions between HSP and the S. aureus SpA protein, which may mediate the binding of RCSAP NPs to S. aureus. In vivo assessments demonstrated that RCSAP NPs significantly accelerates wound healing in S. aureus-infected models, with excellent biocompatibility and minimal systemic toxicity. This work paves the way for all-polyester-based nanomedicines harnessing the power of natural antibacterial and heparin-mimicking agents synergistically for enhanced disinfection and wound healing, curbing drug resistance.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
