Phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents

Abstract

Purpose

Multi- and extensively drug-resistant tuberculosis (TB) is a global threat to human health. It requires immediate action to seek new antitubercular compounds and devise alternate strategies. Nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. In view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria.

Methods

Silver (AgNPs), gold (AuNPs), and gold–silver bimetallic (Au–AgNPs) nanoparticles synthesized from medicinal plants, such as Barleria prionitis, Plumbago zeylanica, and Syzygium cumini, were tested against Mycobacterium tuberculosis and M. bovis BCG. In vitro and ex vivo macrophage infection model assays were designed to determine minimum inhibitory concentration (MIC) and half maximal inhibitory concentration of nanoparticles. Microscopic analyses were carried out to demonstrate intracellular uptake of nanoparticles in macrophages. Besides this, biocompatibility, specificity, and selectivity of nanoparticles were also established with respect to human cell lines.

Results

Au–AgNPs exhibited highest antitubercular activity, with MIC of <2.56 μg/mL, followed by AgNPs. AuNPs did not show such activity at concentrations of up to 100 μg/mL. In vitro and ex vivo macrophage infection model assays revealed the inhibition of both active and dormant stage mycobacteria on exposure to Au–AgNPs. These nanoparticles were capable of entering macrophage cells and exhibited up to 45% cytotoxicity at 30 μg/mL (ten times MIC concentration) after 48 hours. Among these, Au–AgNPs synthesized from S. cumini were found to be more specific toward mycobacteria, with their selectivity index in the range of 94–108.

Conclusion

This is the first study to report the antimycobacterial activity of AuNPs, AgNPs, and Au–AgNPs synthesized from medicinal plants. Among these, Au–AgNPs from S. cumini showed profound efficiency, specificity, and selectivity to kill mycobacteria. These should be investigated further to develop novel TB nanoantibiotics.

Keywords:

• tuberculosis
• mycobacteria
• antimycobacterial agent
• nanoparticles
• drug resistance
• cytotoxicity

Acknowledgments

RS and SW acknowledge the University Grants Commission (UGC), New Delhi, for research fellowship. US thanks UGC for UGC-DS Kothari postdoctoral fellowship. The authors also thank Dr DS Gond, Department of Microbiology, Savitribai Phule Pune University (SPPU), Pune, and Ms Gayatri Salunke, Institute of Bioinformatics and Biotechnology, SPPU, for providing phytogenic nanoparticles for the study.

Disclosure

The authors report no conflicts of interest in this work.