Nanoparticle-Loaded Hydrogel for the Light-Activated Release and Photothermal Enhancement of Antimicrobial Peptides

Rising concerns over multidrug-resistant bacteria have necessitated an expansion to the current antimicrobial arsenal and forced the development of novel delivery strategies that enhance the efficacy of existing treatments. Antimicrobial peptides (AMPs) are a promising antibiotic alternative that physically disrupts the membrane of bacteria, resulting in rapid bactericidal activity; however, clinical translation of AMPs has been hindered by their susceptibility to protease degradation. Through the co-loading of liposomes encapsulating model AMP, IRIKIRIK-CONH₂ (IK8), and gold nanorods (AuNRs) into a poly(ethylene glycol) (PEG) hydrogel, we have demonstrated the ability to protect encapsulated materials from proteolysis and provide the first instance of the triggered AMP release. Laser irradiation at 860 nm, at 2.1 W cm^-2, for 10 min led to the photothermal triggered release of IK8, resulting in bactericidal activity against Gram-negative Pseudonomas aeruginosa and Gram-positive Staphylococcus aureus. Furthermore, by increasing the laser intensity to 2.4 W cm^-2, we have shown the thermal enhancement of AMP activity. The photothermal triggered release, and enhancement of AMP efficacy, was demonstrated to treat two rounds of fresh S. aureus, indicating that the therapeutic gel has the potential for multiple rounds of treatment. Taken together, this novel therapeutic hydrogel system demonstrates the stimuli-responsive release of AMPs with photothermal enhanced antimicrobial efficacy to treat pathogenic bacteria.