Enhanced Nitric Oxide Delivery Through Self-Assembling Nanoparticles for Eradicating Gram-Negative Bacteria

Area of Science:

• Antimicrobial resistance research
• Nanotechnology in medicine
• Bacterial membrane interactions

Background:

• Gram-negative bacteria possess protective outer membranes and efflux pumps, contributing to antibiotic resistance.
• Novel strategies are urgently needed to combat the growing threat of antimicrobial resistance.

Purpose of the Study:

• To develop and evaluate novel nitric oxide (NO) donor nanoparticles (FuNPs) for enhanced antimicrobial activity.
• To investigate the synergistic bactericidal mechanism of FuNPs in combination with polymyxin B (PMB).

Main Methods:

• Synthesis of three furoxan derivatives engineered for self-assembly into NO-donor nanoparticles (FuNPs).
• Evaluation of bactericidal efficacy of FuNPs and PMB against Gram-negative bacteria.
• Mechanism elucidation using confocal, scanning, and transmission electron microscopy, and neutron reflectometry.

Main Results:

• FuNPs combined with PMB demonstrated significantly enhanced bactericidal efficacy at low NO concentrations (0.1-2.8 µg mL⁻¹).
• FuNPs were observed to disrupt bacterial outer membranes by interacting with surface polysaccharides.
• PMB enhanced outer membrane permeability by binding to lipid A, leading to synergistic bacterial killing.

Conclusions:

• Self-assembled NO-donor nanoparticles offer a promising strategy to overcome antibiotic resistance in Gram-negative bacteria.
• The combination of FuNPs and PMB represents a groundbreaking approach for next-generation antimicrobial agents.