Background: Chagas' disease, caused by Trypanosoma cruzi, was described for the first time over a
hundred years ago. Nonetheless, clinically available drugs still lack effective and selective properties. Nitric oxide
(NO) produced by activated macrophages controls the progression of disease by killing the parasite.
Methods and Results: Here, chitosan nanoparticles (CS NPs) were synthesized and mercaptosuccinic acid
(MSA), the NO donor precursor, was encapsulated into CS NPs, forming MSA-CS NPs, which had hydrodynamic
size of 101.0±2.535 nm. Encapsulated MSA was nitrosated forming NO donor S-nitrosomercaptosuccinic
acid-containing nanoparticles (S-nitroso-MSA-CS NPs). Kinetic data revealed a sustained
release of NO from the nanoparticles. S-nitroso-MSA-CS NPs inhibited epimastigote proliferation and trypomastigote
viability of T. cruzi, with IC50=75.0±6.5 µg·mL-1 and EC50=25.0±5.0 µg·mL-1, respectively. Treatment
of peritoneal macrophages with nanoparticles decreased the number of T. cruzi-infected cells and the average
number of intracellular replicative amastigotes per infected cells. Besides, the results have showed a selective
behaviour of S-nitroso-MSA-CS NPs to parasites. Morphological and biochemical changes induced by
these NO-releasing nanoparticles, such as cell shrinkage, cell cycle arrest, mitochondrial membrane depolarization
and phosphatidylserine exposure on cell surface indicate that epimastigotes death is associated to the apoptotic
Conclusion: S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas's disease.