Gelatinase-Responsive Photothermal Nanotherapy Based on Au Nanostars Functionalized with Antimicrobial Peptides for Treating Staphylococcus aureus Infections

As a pathogenic worldwide pathogen, Staphylococcus aureus (S. aureus) has brought great challenges to the prevention and treatment of diseases in the community. Although antimicrobial peptides show potent antibacterial activity because of their unique bactericidal mechanism, their inherent cationic toxicity cannot be ignored. Utilizing the related characteristics of S. aureus to achieve targeted therapy can reduce the toxicity to host cells to a great extent. Herein, we designed Cy7-labeled antimicrobial peptide (GLFVDK(-Cy7)GKRWWKWWRRGPLGVRGC) with S. aureus targeting recognition peptide (GLFVD) and gelatinase cleavage site (PLGVR), which together with SH-PEG was anchored to gold nanostars (AuNS) by the Au–thiol bond to form a photothermal nanoprobe (APA) targeting S. aureus. The size of the generated APA nanoprobe was 201 ± 3.7 nm, and it was nonfluorescent in the physiological environment due to the fluorescence resonance energy transfer between the AuNS core and Cy7. In vitro results showed that in the gelatinase environment secreted by S. aureus, antimicrobial peptides were released from AuNS and restored the fluorescence of Cy7 in situ, targeting and priority killing of S. aureus. In the mouse wound model of double bacterial infection, APA effectively removed S. aureus from the infected site and promoted the rapid healing of infected wounds through gelatinase-responsive drug release and photothermal synergistic antibacterial treatment.