Self-assembly of DOPA-containing peptides for enhanced antimicrobial efficacy and promoted wound healing

Bacterial infection and excessive reactive oxygen species (ROS) accumulation synergistically disrupt the wound microenvironment and severely impair the healing process. Therefore, multifunctional biomaterials with intrinsic antibacterial and antioxidant properties are highly desirable for the effective treatment of infected wounds. Here, we rationally designed and synthesized two DOPA-containing constitutional isomeric peptides with dual antimicrobial and antioxidant activities, each containing one 3,4-dihydroxy-L-phenylalanine (DOPA), four tryptophan residues (W), and three arginine residues (R), and designated as WRWRWRW(DOPA) and WWWWRRR(DOPA), respectively. These peptides can self-assemble in aqueous solutions into different morphologies, with WRWRWRW(DOPA) forming vesicles, whereas WWWWRRR(DOPA) assembles into micelles. Notably, both self-assembled nanostructures exhibited enhanced antibacterial activity compared with their corresponding peptide precursors, and the vesicular assemblies showed superior antimicrobial efficacy relative to their micellar counterparts. Based on these findings, the vesicle-forming peptide system was further investigated for ROS-scavenging capability and wound healing performance. The results demonstrated that the vesicular assemblies possessed efficient ROS elimination capacity and significantly promoted infected wound repair. Overall, this work highlights the critical role played by the morphology of self-assembled nanostructures in regulating antimicrobial and antioxidant performance, providing a promising strategy for the design of multifunctional peptide-based systems for infected wound therapy.