{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:19:34Z","timestamp":1787015974540,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n The interest in nanotechnology applications in medicine, particularly for combating microbial infections, has surged in recent years. This study investigated the in\u00a0vitro and in\u00a0vivo antileishmanial effects of copper nanoparticles (CuNPs) that were green synthesised using\n \n Capparis spinosa<\/jats:italic>\n <\/jats:styled-content>\n fruit extract, both on their own and in conjunction with paromomycin (PM). CuNPs were synthesised from a methanolic extract of\n \n C. spinosa<\/jats:italic>\n <\/jats:styled-content>\n . We assessed the in\u00a0vitro antileishmanial activity of CuNPs (10\u2013200\u2009\u03bcg\/mL) as well as the same concentrations of CuNPs (10\u2013200\u2009\u03bcg\/mL) combined with PM (10\u2013200\u2009\u03bcg\/mL), targeting the promastigote and amastigote forms of\n Leishmania major<\/jats:italic>\n . Additionally, we evaluated the cytotoxic effects of CuNPs on THP1 cells. Subsequently, we tested these formulations on female BALB\/c mice infected with\n \n L. major<\/jats:italic>\n <\/jats:styled-content>\n . The study measured footpad swelling, quantified parasite load through real\u2010time PCR, and assessed levels of cytokines such as interleukin\u20104 (IL\u20104) and gamma interferon (IFN\u2010\u0264), nitric oxide (NO), and arginase (ARG). The results demonstrated that CuNPs, particularly when combined with PM, significantly inhibited (\n p<\/jats:italic>\n \u2009<\u20090.001) the growth of\n \n L. major<\/jats:italic>\n <\/jats:styled-content>\n promastigotes and amastigotes and stimulated IFN\u2010\u0264, NO production and reduced IL\u20104 and ARG levels (\n p<\/jats:italic>\n \u2009<\u20090.05). Importantly, CuNPs exhibited minimal cytotoxicity towards THP1 cells. In infected mice, the treatment with CuNPs, notably in combination with PM, resulted in a significant (\n p<\/jats:italic>\n \u2009<\u20090.05) reduction in the mean number of parasites. Treatment with CuNPs at concentrations of 100 and 200\u2009mg\/mL led to a decrease in lesion diameter. The results of this study highlight the potent antileishmanial activity and synergistic effects of CuNPs, both alone and in combination with PM, against\n \n L. major<\/jats:italic>\n <\/jats:styled-content>\n promastigotes and amastigote forms, as well as their potential in treating cutaneous leishmaniasis (CL) in BALB\/c mice.\n <\/jats:p>","DOI":"10.1111\/pim.70017","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:04:01Z","timestamp":1753088641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Effect of Copper Nanoparticles and Paromomycin in the Treatment of Cutaneous Leishmaniasis"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6954-7942","authenticated-orcid":false,"given":"Maryam","family":"Heidari\u2010Kharaji","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, College of Veterinary Medicine University of Missouri Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Montreal Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Ferreira","sequence":"additional","affiliation":[{"name":"McGill University Health Center Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robinson Pavene","family":"Pooneiad","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Sajid","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Missouri Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11120.1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2000.00664.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2019.108976"},{"issue":"2","key":"e_1_2_7_5_1","first-page":"e66527","article-title":"Herbal Drugs With Promising Anti\u2010Leishmanial Activity: New Hope for Leishmaniasis Treatment","volume":"3","author":"Heidari\u2010Kharaji M.","year":"2016","journal-title":"Journal of Skin and Stem Cell"},{"key":"e_1_2_7_6_1","volume-title":"Tropical Medicine & International Health","author":"Badirzadeh A.","year":"2015"},{"issue":"1","key":"e_1_2_7_7_1","first-page":"1","article-title":"Current Treatment of Leishmaniasis: A Review","volume":"1","author":"Monzote L.","year":"2009","journal-title":"Open Antimicrobial Agents Journal"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2011.02.007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-008-0943-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007843"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13010"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.13068"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.70002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2013.07.011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S127683"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-013-5422-8"},{"key":"e_1_2_7_17_1","first-page":"358","article-title":"Drug Resistance in Malaria, Tuberculosis, and HIV in South East Asia: Biology, Programme, and Policy Considerations","volume":"3545","author":"Panda S.","year":"2017","journal-title":"British Medical Journal"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70011-6"},{"issue":"70","key":"e_1_2_7_19_1","article-title":"A Parasite Rescue and Transformation Assay for Antileishmanial Screening Against Intracellular Leishmania Donovani Amastigotes in THP1 Human Acute Monocytic Leukemia Cell Line","volume":"4054","author":"Jain S. 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