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The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle\u2013polyvinylpyrrolidone-[meglumine antimoniate (Glucantime\u00ae)]) nanocomposite during<jats:italic>Leishmania amazonensis<\/jats:italic>infection<jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the<jats:italic>Leishmania<\/jats:italic>parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-\u03b1 and MIP-1\u03b1 levels increased significantly, while the IL-17\u00a0A level decreased significantly after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12866-021-02267-2","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T12:02:34Z","timestamp":1626091354000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages"],"prefix":"10.1186","volume":"21","author":[{"given":"Ana Patricia Cacua","family":"G\u00e9lvez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio Pican\u00e7o","family":"Diniz Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca Thereza Silva Santa","family":"Br\u00edgida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Drummond","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"2267_CR1","volume-title":"Manual de procedimientos para la vigilancia y control de las leishmaniasis en las Am\u00e9ricas","author":"Organizaci\u00f3n Panamericana de la Salud (OPAS)","year":"2019","unstructured":"Organizaci\u00f3n Panamericana de la Salud (OPAS). 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