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

Antimicrobial peptides (AMPs), such as Temporin-FL, exhibit promising antibacterial activity against Staphylococcus aureus. 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 in vitro revealed enhanced intracellular bacterial clearance in HaCaT cells, while the in vivo 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.