Atividade imunomoduladora e leishmanicida de nanopartículas de óxido de zinco dopadas com prata

Abstract

In recent decades, the use of nanoparticles (NP) in biomedical research has grown exponentially, especially against intracellular pathogens - such as those causing leishmaniasis - and in the modulation of immune cells. In this context, tegumentary leishmaniasis TL, transmitted by sandflies and affecting the integuments, cause an important set of clinical manifestations which has been a relevant public health problem. TL causes from single or multiple lesions in the integuments, which can impair the individual's quality of life, to disfiguring and life-threatening lesions. Every year, there are an estimated 700 thousand to 1.2 million new cases of TL and, even so, there are few studies or treatments against this pathology. In this context, the intracellular parasite L. braziliensis has been one of the main causes of this group of diseases. It is known that one of the main predictors of the severity of infection by parasites of the L. genus is the host's immune system (IS), therefore therapies aimed at its immune modulation can be used to limit and combat such diseases. The present study proposed to test pure zinc oxide NP (ZnO) or hybrid ZnO NP doped with 5%, 9% or 11% silver (Ag) (ZnO:5Ag, ZnO:9Ag and ZnO:11Ag, respectively) as to its capacity to inhibit L. braziliensis strains and also to observe the immunomodulatory potential of these NPs. Our findings showed that all tested NPs have selectivity to cause the death of L. braziliensis promastigotes when compared to RAW 264.7 cells, in addition to their ability to inhibit the growth and replication of the parasite in question. ZnO:9Ag was the NP with the best leishmanicidal potential (IC50 = 7,93 μg/mL), with the ability to inhibit the growth of the parasite from the third day of treatment. Accordingly, NPs, especially ZnO:9Ag, were able to modulate the IS to a pro-inflammatory profile, with an increase in surface molecules, indicating the assembly of an inflammatory response of T cells and increased production of inflammatory cytokines. These results indicate that these NP, especially ZnO:9Ag, are potential therapeutic targets to treat diseases caused by parasites of the genus L., in particular, L. braziliensis. Further studies are needed to elucidate other aspects of both the SI with these nanoformulations and the relationship between parasite and NP.