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

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 (IC50) values in the range of 0.03-0.035 mu g/mL. The IC50 values of the BNPs are much lower compared to those of miltefosine (IC50 = 10 mu g/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.