Dual stimuli-responsive metal-organic framework-based nanosystem for synergistic photothermal/pharmacological antibacterial therapy

Abstract

The serious threat of drug-resistant bacterial pathogens has arisen through overuse of antibiotics. Photothermal therapy (PTT) has come to prominence as viable alternative strategy for antibacterial therapy. In this work, we report a NIR/pH dual stimuli-responsive antibacterial formulation based on zeolitic imidazolate frameworks-8 (ZIF-8) with strong antibacterial activity that combines photothermal heating with enhanced antibiotic delivery. ZIF-8 with polydopamine (PDA) surface modification was used to encapsulate the antibiotic vancomycin to construct a dual stimuli-responsive antimicrobial formulation (Van@ZIF-8@PDA). This treatment was tested against Gram-positive Mu50 (a vancomycin-intermediate S. aureus reference strain). Results showed that the PDA coating improved ZIF-8 stability and dispersion, while also conferring a high photothermal conversion efficiency. Hyperthermia activated by near-infrared (NIR) light irradiation, in conjunction with pH-dependent nanoparticle degradation to release vancomycin, enabled tight control of drug delivery that functioned synergistically in the elimination of both planktonic bacteria prior to biofilm formation and established biofilms. We found that this combined formulation compromises cell structure while also degrading bacterial DNA. Moreover, further investigation showed that the Van@ZIF-8@PDA nanoparticles exhibit good biocompatibility, with low toxicity toward host organs and tissues, while also reducing the antibiotic concentration needed for effective bacterial control. Finally, we treated Mu50 in a mouse model of skin abscess and found that Van@ZIF-8@PDA was effective and safe in vivo. Cumulatively, this study shows that this NIR/pH dual stimuli-responsive nanoparticle-based formulation offers a promising potential strategy for clinical application against bacterial infection that circumvents antibiotic resistance.

Keywords: Mu50; Photothermal therapy (PTT); Polydopamine (PDA); Subcutaneous abscess; Zeolitic imidazolate framework-8 (ZIF-8).