Gallium-based metal–organic frameworks loaded with antimicrobial peptides for synergistic killing of drug-resistant bacteria

Abstract

Increased antibiotic resistance has made bacterial infections a global concern, which requires novel non-antibiotic-dependent antibacterial strategies to address the menace. Antimicrobial peptides (AMPs) are a promising antibiotic alternative, whose antibacterial mechanism is mainly to destroy the membrane of bacteria. Gallium ions exhibit an antibacterial effect by interfering with the iron metabolism of bacteria. With the rapid development of nanotechnology, it is worth studying the potential of gallium-AMP-based nanocomposites for treating bacterial infections. Herein, novel gallium-based metal-organic frameworks (MOFs) were synthesized at room temperature, followed by <i>in situ</i> loading of the model AMP melittin. The obtained nanocomposites exhibited stronger antibacterial activity than pure MEL and gallium ions, achieving the effects of "one plus one is greater than two". Moreover, the nanocomposites showed favorable biocompatibility and accelerated healing of a wound infected by methicillin-resistant <i>Staphylococcus aureus</i> by down-regulation of inflammatory cytokines IL-6 and TNF-α. This work presents an innovative antibacterial strategy to overcome the antibiotic resistance crisis and expand the application of AMPs.