title: Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation.
abstract: In Leishmania the glutathione/glutathione reductase eukaryotic redox sys-tem is replaced by the unique trypanothione/trypanothione reductase (TR) system. In vitro, silver is a more effective TR inhibitor than antimony, the first line drug against leishmaniasis in most endemic countries, and its mechanism of inhibition is similar to that of Sb(III). In particular, silver binds with high affinity to the catalytic triad Cys52, Cys57, and His461', thereby inhibiting TR. Here, Ag(0) activity was tested on the promastigote and amastigote stages of Leishmania infantum using a drug-delivery system consisting in Ag(0) nanoparticles encapsulated by ferritin molecules (PfFt-AgNPs). These were able to induce an antiproliferative effect on the parasites at metal concentrations lower than those used with antimony.
authors.affiliation: Institute of Molecular Biology and Pathology CNR, and Department of Biochemical Sciences, Sapienza University of Roma , P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Baiocco
authors.affiliation: Institute of Molecular Biology and Pathology CNR, and Department of Biochemical Sciences, Sapienza University of Roma , P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ilari
authors.affiliation: Institute of Molecular Biology and Pathology CNR, and Department of Biochemical Sciences, Sapienza University of Roma , P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Ceci
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità , Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Orsini
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità , Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Gramiccia
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità , Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Trentina
authors.initials: T
authors.lastname: Di Muccio
authors.affiliation: Institute of Molecular Biology and Pathology CNR, and Department of Biochemical Sciences, Sapienza University of Roma , P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Colotti
keywords: Leishmania; Trypanothione reductase; drug delivery; nanoparticles; silver