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 a 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 triggered release of AMPs. Laser irradiation at 860 nm, at 2.1 W cm-2, for 10 mins 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 the therapeutic gel has the potential for multiple rounds of treatment. Taken together, this novel therapeutic hydrogel system demonstrates stimuli-responsive release of AMPs with photothermal enhanced antimicrobial efficacy in order to treat pathogenic bacteria.