Synergistic Photodynamic/Antibiotic Therapy with Photosensitive MOF-Based Nanoparticles to Eradicate Bacterial Biofilms

Abstract

Bacterial biofilms pose a serious threat to human health, as they prevent the penetration of antimicrobial agents. Developing nanocarriers that can simultaneously permeate biofilms and deliver antibacterial agents is an attractive means of treating bacterial biofilm infections. Herein, photosensitive metal–organic framework (MOF) nanoparticles were developed to promote the penetration of antibiotics into biofilms, thereby achieving the goal of eradicating bacterial biofilms through synergistic photodynamic and antibiotic therapy. First, a ligand containing benzoselenadiazole was synthesized and incorporated into MOF skeletons to construct benzoselenadiazole-doped MOFs (Se-MOFs). The growth of the Se-MOFs could be regulated to obtain nanoparticles (Se-NPs) in the presence of benzoic acid. The singlet oxygen (1O2) generation efficiencies of the Se-MOFs and Se-NPs were evaluated. The results show that the Se-NPs exhibited a higher 1O2 generation efficacy than the Se-MOF under visible-light irradiation because the small size of the Se-NPs was conducive to the diffusion of 1O2. Afterward, an antibiotic drug, polymyxin B (PMB), was conjugated onto the surface of the Se-NPs via amidation to yield PMB-modified Se-NPs (PMB-Se-NPs). PMB-Se-NPs exhibit a synergistic antibacterial effect by specifically targeting the lipopolysaccharides present in the outer membranes of Gram-negative bacteria through surface-modified PMB. Benefiting from the synergistic therapeutic effects of antibiotic and photodynamic therapy, PMB-Se-NPs can efficiently eradicate bacterial biofilms at relatively low antibiotic doses and light intensities, providing a promising nanocomposite for combating biofilm infections.