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Talita Katiane Brito, 1, 2,* Rony Lucas Silva Viana, 2, 3,* Cláudia Jassica Gonçalves Moreno, 3, 4 Jefferson da Silva Barbosa, 1, 2, 5 Francimar Lopes de Sousa Júnior, 6 Mayara Jane Campos de Medeiros, 6 Raniere Fagundes Melo-Silveira, 2, 3 Jailma Almeida-Lima, 1–3 Daniel de Lima Pontes, 6 Marcelo Sousa Silva, 3, 4, 7 Hugo Alexandre Oliveira Rocha 1–3 1Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59012-570, Brazil; 2Laboratory of Biotechnology of Natural Polymers (BIOPOL), Department of Biochemistry, Center of Biosciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59078-970, Brazil; 3Postgraduate Program in Biochemistry, Federal University of Rio Grande do Norte UFRN), Natal, Rio Grande do Norte 59078-970, Brazil; 4Laboratory of Immunoparasitology, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59012-570, Brazil; 5Federal Institute of Education, Science and Technology of Rio Grande do Norte (IFRN), Natal, Rio Grande do Norte 59500-000, Brazil; 6Laboratory of Chemistry of Coordination and Polymers (LQCPol), Institute of Chemistry, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59078-970, Brazil; 7Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, New University of Lisbon, Lisboa 1349-008, Portugal*These authors contributed equally to this workCorrespondence: Hugo Alexandre Oliveira RochaLaboratory of Biotechnology of Natural Polymers (BIOPOL), Department of Biochemistry, Center of Biosciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte 59078-970, BrazilEmail hugo@cb.ufrn.brBackground: Chagas disease, also known as American Trypanosomiasis, is caused by the protozoan Trypanosoma cruzi. It is occurring in Americas, including USA and Canada, and Europe and its current treatment involves the use of two drugs as follows: benznidazole (BNZ) and nifurtimox, which present high toxicity and low efficacy during the chronic phase of the disease, thus promoting the search for more effective therapeutic alternatives. Amongst them xylan, a bioactive polysaccharide, extracted from corn cob.Methods: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FITR), Raman spectroscopy, energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy, atomic force microscopy, plasma optical emission spectroscopy (ICP-OES), dynamic light scattering (DLS) have been used to characterize the silver-xylan nanoparticles (NX). Their cytotoxicity was evaluated with 3-bromo(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test. MTT and flow cytometry were used to ascertain the anti-Trypanosoma cruzi activity.Results: UV-Vis spectroscopy gave plasmon resonance ranging between 400 and 450 nm while FITC and Raman spectroscopy proved nano interface functionalized with xylan. ICP-OES data showed NX with xylan (81%) and silver (19%). EDS showed NX consisting of carbon (59.4%), oxygen (26.2%) and silver (4.8%) main elements. Spherical NX of 55 nm average size has been depicted with SEM and AFM, while DLS showed 102 ± 1.7 nm NX. The NX displayed negligible cytotoxicity (2000 μg/mL). NX (100 μg/mL) was more effective, regardless of experiment time, in affecting the ability of parasites to reduce MTT than BZN (100 μg/mL). In addition, NX (100 μg/mL) induced death of 95% of parasites by necrosis.Conclusion: This is the first time silver nanoparticles are presented as an anti-Trypanosoma cruzi agent and the data point to the potential application of NX to new preclinical studies in vitro and in vivo.Keywords: xylan, silver nanoparticles, Trypanosoma cruzi, benznidazole