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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Application of magnetically induced hyperthermia in the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections

Texto completo
Autor(es):
Grazu, V. [1] ; Silber, A. M. [2] ; Moros, M. [1] ; Asin, L. [1] ; Torres, T. E. [1, 3, 4] ; Marquina, C. [3, 5] ; Ibarra, M. R. [1, 3] ; Goya, G. F. [1, 3]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Zaragoza, INA, Zaragoza 50018 - Spain
[2] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, Sao Paulo - Brazil
[3] Univ Zaragoza, Fac Ciencias, Dept Fis Mat Condensada, Zaragoza 50018 - Spain
[4] Univ Zaragoza, LMA, Zaragoza 50018 - Spain
[5] Univ Zaragoza, CSIC, ICMA, Zaragoza 50018 - Spain
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 7, p. 5351-5360, 2012.
Citações Web of Science: 18
Resumo

Background: Magnetic hyperthermia is currently a clinical therapy approved in the European Union for treatment of tumor cells, and uses magnetic nanoparticles (MNPs) under time-varying magnetic fields (TVMFs). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, given that the therapeutic drugs available have severe side effects and that there are drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe3O4 MNPs in order to provoke cell death remotely using TVMFs. Methods: Iron oxide MNPs with average diameters of approximately 30 nm were synthesized by precipitation of FeSO4 in basic medium. The MNPs were added to C. fasciculata choanomastigotes in the exponential phase and incubated overnight, removing excess MNPs using a DEAE-cellulose resin column. The amount of MNPs uploaded per cell was determined by magnetic measurement. The cells bearing MNPs were submitted to TVMFs using a homemade AC field applicator (f = 249 kHz, H = 13 kA/m), and the temperature variation during the experiments was measured. Scanning electron microscopy was used to assess morphological changes after the TVMF experiments. Cell viability was analyzed using an MTT colorimetric assay and flow cytometry. Results: MNPs were incorporated into the cells, with no noticeable cytotoxicity. When a TVMF was applied to cells bearing MNPs, massive cell death was induced via a nonapoptotic mechanism. No effects were observed by applying TVMF to control cells not loaded with MNPs. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Conclusion: As a proof of principle, these data indicate that intracellular hyperthermia is a suitable technology to induce death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies combating parasitic infection. (AU)

Processo FAPESP: 08/57596-4 - Metabolismo de aminoácidos de Trypanosoma cruzi: alvos putativos para terapia
Beneficiário:Ariel Mariano Silber
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 11/50631-1 - Metabolismo de histidina: o papel da via histina-glutamato na biologia do Trypanosoma cruzi
Beneficiário:Ariel Mariano Silber
Linha de fomento: Auxílio à Pesquisa - Regular