Chelating silica nanoparticles for efficient antibiotic delivery and particle imaging in Gram-negative bacteria

Abstract

The inefficacy of antibiotics against Gram-negative bacteria is a major challenge for treatment of many clinically important bacterial infections. The complex structure of the double cell membrane of Gram-negative bacteria makes it inaccessible to many key antibiotics such as vancomycin and also presents a major challenge for drug development. In this study we design of a novel hybrid silica nanoparticle system bearing membrane targeting groups with the antibiotic encapsulated together with a ruthenium luminescent tracking agent, for optical detection of the nanoparticle delivery in the bacterial cell. The hybrid system shows delivery of vancomycin and efficacy against a library of Gram negative bacterial species. Evidence of penetration of nanoparticles in bacteria cells is achieved via luminescence of the ruthenium signal. Our studies show that nanoparticles modified with aminopolycarboxylate chelating groups are an effective delivery system in bacterial growth inhibition in species whereas the molecular antibiotic is ineffective. This design provides a new platform for delivery of antibiotics that cannot alone penetrate the bacterial membrane.