title: Phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology, Savitribai Phule Pune University, Pune, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Singh
authors.affiliation: Combichem-Bioresource Center, Organic Chemistry Division, National Chemical Laboratory, Pune, India.
authors.forename: Laxman
authors.initials: L
authors.lastname: Nawale
authors.affiliation: Combichem-Bioresource Center, Organic Chemistry Division, National Chemical Laboratory, Pune, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Arkile
authors.affiliation: Department of Microbiology, Savitribai Phule Pune University, Pune, India.
authors.forename: Sweety
authors.initials: S
authors.lastname: Wadhwani
authors.affiliation: Department of Microbiology, Savitribai Phule Pune University, Pune, India.
authors.forename: Utkarsha
authors.initials: U
authors.lastname: Shedbalkar
authors.affiliation: Department of Microbiology, Savitribai Phule Pune University, Pune, India.
authors.forename: Snehal
authors.initials: S
authors.lastname: Chopade
authors.affiliation: Combichem-Bioresource Center, Organic Chemistry Division, National Chemical Laboratory, Pune, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Sarkar
authors.affiliation: Department of Microbiology, Savitribai Phule Pune University, Pune, India; Dr Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India.
authors.forename: Balu Ananda
authors.initials: BA
authors.lastname: Chopade
mesh_terms: D027901:Acanthaceae / Q000737:chemistry; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006046:Gold / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D029606:Plumbaginaceae / Q000737:chemistry; D012834:Silver / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D012834:Silver; D006046:Gold
keywords: antimycobacterial agent; cytotoxicity; drug resistance; mycobacteria; nanoparticles; tuberculosis