Polyaminoglycoside nanosystem expressing antimicrobial peptides for multistage chronic wound management

Chronic wounds are difficult to heal due to pathogenic microbial colonization and dysregulation of healing cascades, necessitating novel therapeutic strategies. This study developed a multifunctional nanosystem by integrating the antimicrobial peptide LL37 with cationic polyaminoglycoside (SS-HPT), constructing a self-sustaining "AMP factory” to achieve multi-stage modulation of the wound healing. Validation through cell-level experiments and in vivo dual models (mechanical injury and bacterial infection) in immunocompromised rats demonstrated the system's unique dual intracellular-extracellular pathogen-killing capability, significantly accelerating the wound healing process. Transcriptomic analysis revealed that its mechanism involves the dual effects of suppressing pro-inflammatory factor expression and activating tissue repair pathways. Histological evidence confirmed that the system promotes angiogenesis, enhances re-epithelialization rates, and guides orderly collagen fiber deposition. This nanosystem, combining efficient AMP delivery and integrated therapeutic strategies, achieves three-dimensional synergy in microbial clearance, immune microenvironment regulation, and tissue matrix remodeling, providing theoretical and technical foundations for a paradigm shift in chronic wound treatment.