Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites.

The genus Leishmania consists of over 20 different species causing a spectrum of disease symptoms categorized as cutaneous, mucocutaneous, or visceral leishmaniasis. No vaccine is available in humans, and current drug regimens suffer from low efficacy, associated toxicities, and are increasingly becoming side-lined by drug resistance. Because of this, the development of new therapeutics is desperately needed. Recent years, the therapeutic use of nanotechnology has increased exponentially. The biogenic synthesis of these nanostructures creates particles similar to those chemically synthesized but are often more environmentally safe, cost-effective, and allow for increased control over size, shape, and composition. Here, we provided a review of the current publications using the biogenic synthesis of nanoparticles particularly focusing on those used in the treatment of leishmaniasis published from January 1, 2010, to April 30, 2025. The documents were analyzed by applying criteria such as nanometal type, source of green synthesis (plant or microorganism), nanoparticles size, Leishmania species (sp.) and stage (promastigote or amastigote), cytotoxicity, and in vivo studies. A total of 50 articles were analyzed. Among biogenic nanoparticles (NPs), silver NPs were the most extensively studied (15 studies), while Leishmania tropica (L. tropica) was the most frequently investigated sp. Plant material was the most sources starting material for green synthesis. Produced NPs’ size varied between 2 and 500 nm. Regarding the effect of NPs on Leishmania parasites, most were done in vitro, and only 5 in vivo studies (10%) reported. Moreover, leishmanicidal effects were reported via oxidative stress, mainly through production of reactive oxygen species and nitrogen radical species. In general, green synthesis produced NPs with smaller sizes, larger surface area to volume ratios, and better internalization by the cells. Thus, green synthesis of NPs could be a promising option to resolve current treatment safety and efficacy concerns while also maintaining accessibility in low- and middle-income countries.