Cesar Armando Contreras Lancheros, Milena Trevisan Pelegrino, Danielle Kian, Eliandro Reis Tavares, Priscila Mazzochi Hiraiwa, Samuel Goldenberg, Celso Vataru Nakamura, Lucy Megumi Yamauchi, Phileno Pinge-Filho, Amedea Barozzi Seabra* and Sueli Fumie Yamada-Ogatta* Pages 830 - 839 ( 10 )
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 pathway.
Conclusion: S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas's disease.
Antiprotozoal activity, chitosan nanoparticles, nitric oxide nanocarrier, S-nitroso mercaptosuccinic acid, cell death, Chagas' disease.
Departamento de Microbiologia, Centro de Ciencias Biologicas, Universidade Estadual de Londrina. Rodovia Celso Garcia Cid s/n, Campus Universitario, 86051-980, Londrina, Parana, Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC. Avenida dos Estados 5001, Santa Terezinha, 09210-580, Santo Andre, Sao Paulo, Departamento de Microbiologia, Centro de Ciencias Biologicas, Universidade Estadual de Londrina. Rodovia Celso Garcia Cid s/n, Campus Universitario, 86051-980, Londrina, Parana, Bolsista do Programa Nacional de Pos-Doutorado da Coordenacao de Aperfeicoamento de Pessoal de Nível Superior – PNPD/CAPES. Ministry of Education, Rio de Janeiro, RJ, Instituto Carlos Chagas, FIOCRUZ. Rua Professor Algacyr Munhoz Mader, 3775, Cidade Industrial, 81350- 010, Curitiba, Parana, Instituto Carlos Chagas, FIOCRUZ. Rua Professor Algacyr Munhoz Mader, 3775, Cidade Industrial, 81350- 010, Curitiba, Parana, Departamento de Ciencias Basicas da Saude, Centro de Ciencias da Saude, Universidade Estadual de Maringa. Avenida Colombo 5790, 87020-900, Maringa, Parana, Departamento de Microbiologia, Centro de Ciencias Biologicas, Universidade Estadual de Londrina. Rodovia Celso Garcia Cid s/n, Campus Universitario, 86051-980, Londrina, Parana, Departamento de Ciencias Patologicas, Centro de Ciencias Biologicas, Rodovia Celso Garcia Cid s/n, Campus Universitario, 86051-980, Londrina, Parana, Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC. Avenida dos Estados 5001, Santa Terezinha, 09210-580, Santo Andre, Sao Paulo, Departamento de Microbiologia, Centro de Ciencias Biologicas, Universidade Estadual de Londrina. Rodovia Celso Garcia Cid s/n, Campus Universitario, 86051-980, Londrina, Parana