Mesoporous silica nanoparticles containing silver as novel antimycobacterial agents against Mycobacterium tuberculosis

TL;DR

This study develops mesoporous silica nanoparticles loaded with silver compounds as a novel, effective, and potentially safer antimycobacterial agent against resistant Mycobacterium tuberculosis strains, demonstrating promising in vitro results.

Contribution

Introduces two new mesoporous silica nanoparticle systems carrying silver compounds as targeted antimycobacterial agents, enhancing delivery and efficacy against Mtb.

Findings

Both nanosystems showed good antimycobacterial activity.

Silver bromide containing system had lower MIC.

Cryo-EM revealed damage to mycobacterial cell envelope.

Abstract

Tuberculosis remains today a major public health issue with a total of 9 million new cases and 2 million deaths annually. The lack of an effective vaccine and the increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics, anticipate a complicated scenario in the near future. The use of nanoparticles features as an alternative to antibiotics in tackling this problem due to their potential effectiveness in resistant bacterial strains. In this context, silver nanoparticles have demonstrated high bactericidal efficacy, although their use is limited by their relatively high toxicity, which calls for the design of nanocarriers that allow silver based nanoparticles to be safely delivered to the target cells or tissues. In this work mesoporous silica nanoparticles are used as carriers of silver based nanoparticles as antimycobacterial agent against Mtb. Two different synthetic approaches have been used to afford, on the one hand, a 2D hexagonal mesoporous silica nanosystem which contains silver bromide nanoparticles distributed all through the silica network and, on the other hand, a core@shell nanosystem with metallic silver nanoparticles as core and mesoporous silica shell in a radial mesoporous rearrangement. Both materials have demonstrated good antimycobacterial capacity in in vitro test using Mtb, being lower the minimum inhibitory concentration for the nanosystem which contains silver bromide. Therefore, the interaction of this material with the mycobacterial cell has been studied by cryo-electron microscopy, establishing a direct connection between the antimycobactericidal effect observed and the damage induced in the cell envelope.