Delivery of Temporin-FL via Mesoporous Polydopamine Nanoparticles Enhances Antimicrobial Penetration and Accelerates Healing in <i>Staphylococcus aureus</i> -Infected Wounds

Antimicrobial peptides (AMPs), such as Temporin-FL, exhibit promising antibacterial activity against <i>Staphylococcus aureus</i>. However, their clinical application is hindered by rapid degradation in wound environments and poor bioavailability. To address these limitations, we developed mesoporous polydopamine nanoparticles (MPDA) for the skin-targeted delivery of Temporin-FL. MPDA was synthesized via a one-pot polymerization method, with structural characterization confirming uniform mesopores (∼10 nm) and high surface area (320 m²/g). Subsequently, Temporin-FL was loaded into MPDA (MPDA@Temporin-FL), achieving a 61.04% encapsulation efficiency. Notably, the nanocomposite demonstrated a pH-responsive drug release, mimicking the acidic microenvironment of infected wounds. The studies <i>in vitro</i> revealed enhanced intracellular bacterial clearance in HaCaT cells, while the <i>in vivo</i> experiments using murine full-thickness wound models showed superior skin penetration and accelerated healing. Importantly, histological analysis highlighted robust granulation tissue formation and collagen deposition in the MPDA@Temporin-FL group, concomitantly with reduced pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Collectively, these results underscore the dual functionality of MPDA@Temporin-FL: targeted antimicrobial delivery and tissue regenerative modulation. Therefore, this nanoplatform represents a clinically translatable strategy to combat antibiotic-resistant infections while promoting wound repair, addressing critical gaps in current AMP-based therapies.