Gold–Silver Bimetallic Nanoparticles Reduced with Herbal Leaf Extracts Induce ROS-Mediated Death in Both Promastigote and Amastigote Stages of Leishmania donovani

Abstract

Resistance to antileishmanial drugs such as sodium stibogluconate (SSG), amphotericin B (Amp-B), and miltefosine is on the rise, and alternate strategies for effective treatment have gained importance in recent years. Although nanoparticle (NP)based composite drugs that have emerged recently have been found to be effective, the associated toxicity limits their usage. Bimetallic NPs produced through reduction with medicinal plant extracts are proposed to overcome the toxicity of the NPs. In the present study, three types of gold−silver bimetallic nanoparticles (Au−Ag BNPs) were synthesized through a single-step reduction process using fenugreek, coriander, and soybean leaf extracts. All of the three types of BNPs exhibited high antileishmanial effects against promastigotes with half-inhibitory concentration (IC 50 ) values in the range of 0.03−0.035 μg/mL. The IC 50 values of the BNPs are much lower compared to those of miltefosine (IC 50 = 10 μg/mL). The synthesized BNPs induced the reactive oxygen species (ROS)mediated apoptosis-like death in the promastigotes and could potentiate the antileishmanial activity of macrophages. The intracellular amastigotes were reduced by 31−46% in macrophages. The biogenic BNPs synthesized in this study and their potent antileishmanial activity provide further impetus to the ongoing quest for novel drugs to effectively manage leishmaniasis.

Green Approach: ‘‘A Forwarding Step for Curing Leishmaniasis—A Neglected Tropical Disease’’

“…Keeping in view the effective antimicrobial activities of silver metal, silver/silver oxide NPs synthesized using a variety of medicinally important plant species, including Mentha arvensis L., Ficus benghalensis, Cuminum cyminum, Moringa oleifera, Silybum marianum, and Sechium edule, at a dosage of 10, 300, 0.5, 246, and 51.88 μg/ml tested against L. tropica, L. donovani, L. tropica, L. major, L. tropica, and Leishmania donovani, respectively (Baranwal et al, 2018;El-Khadragy et al, 2018;Hameed et al, 2019;Ismail et al, 2019;Bagirova et al, 2020;Javed et al, 2020). Gold and silver bimetallic NPs synthesized by using medically important plants have also been reported to be used for the prevention of this disease (Alti et al, 2020). However, Cannabis sativa-based Au-NPs accomplished virtuous antileishmanial activity against amastigote forms (IC 50 : 171•00 ± 2•28 μg/ml) (Hameed et al, 2020).…”

“…Phytosynthesized NPs revealed an identical effect on the inhibition of parasitic growth at a comparatively lesser concentration than the prescribed dose of Amp B to cure this disease. Additionally, bimetallic nanoparticles including Au−Ag, Zn−Ag, and Ti−Ag were synthesized using the green approach and proficiently used as a therapeutic source to treat leishmaniasis (Alti et al, 2020). NPs are preferred over other therapeutic sources to treat this dreaded disease because of their nontoxic, harmless, and efficient delivery system for vaccine.…”

“…Owing to the small size of NPs (1-100 nm), the ability to penetrate easily into the cells, extensive circulation within the body, and the efficient targeted drug delivery system, they can be reflected as a better medication to treat endemic leishmaniasis (Ebrahimi et al, 2017). Further, plant-based nanoparticles have been reported as a successful approach for the preclusion of microbial infections as well as in the treatment of leishmaniasis (Alti et al, 2020). Owing to the green and eco-friendly nature, cost effectiveness, less hazardous nature, and involvement of phytoconstituents for capping and stabilization, plant-based metal oxide nanoparticles (NPs) (silver, zinc, nickel, iron, etc.)…”

“…Owing to the green and eco-friendly nature, cost effectiveness, less hazardous nature, and involvement of phytoconstituents for capping and stabilization, plant-based metal oxide nanoparticles (NPs) (silver, zinc, nickel, iron, etc.) have been in use to cure leishmanial infection (Ismail et al, 2019;Alti et al, 2020). The present review focuses on the use of plantbased natural products, the phytosynthesized NPs, to cure Leishmania.…”

Synthesis of Au, Ag, and Au–Ag Bimetallic Nanoparticles Using Pulicaria undulata Extract and Their Catalytic Activity for the Reduction of 4-Nitrophenol

“…Bimetallic Au–Ag NPs have been prepared with Azadirachta indica leaf broth [ 25 ], and Gopinath et al prepared spherical Au–Ag NPs (average size 20 nm) using Gloriosa superba leaf extracts [ 26 ]. Recently, three types of Au–Ag bimetallic NPs were prepared by using leaf extracts of fenugreek, coriander, and soybean as reducing agents in a single-pot reduction process [ 27 ]. Similarly, Sharma et al used an aqueous extract of clove buds to prepare Au–Ag bimetallic NPs [ 28 ].…”