Preparação de nanoestruturas híbridas de ouro e seus efeitos na bioenergética mitocondrial

Abstract

Gold nanorods (AuNRs) are promising nanomaterials for applications in biomedicine due to their singular optical properties and potential of surface modifications. Recently, studies have evaluated the use of AuNRs for selective death of cancer cells by mitochondrial damage. In this present study, AuNRs capped with bovine serum protein (BSA) were synthesized and their effect on the mitochondrial bioenergetics were evaluated. AuNRs were synthesized by the seed mediated method in the presence of cetiltrimethylammonium bromide (CTABr), and incubated with BSA at pH 7.4. The AuNRs thus obtained were characterized by UV-vis spectroscopy, Dynamic light scattering (DLS) and Transmission electron microscopy (TEM). The UV-vis absorption spectra showed the presence of typical AuNRs. After the treatment with BSA the longitudinal surface plasmon resonance was changed in ca. 20 nm red shift nearinfrared. That was an evidence of presence of BSA on to AuNRs surface. The DLS characterization and TEM images showed no significant changes in AuNRs dimensions (ca. 11 x 42 nm) after the addition of BSA. We verified AuNRs effects in vitro at isolated rat liver mitochondria in a dose-dependent manner (6.25 - 100 µM) at mitochondrial respiratory rates parameters (complex I), membrane potential (Δψ), mitochondrial swelling, reactive oxygen species (ROS) production, and TEM. In these results, AuNRs decreased respiratory control ratio by decreasing phosphorylation state (V3) and uncoupled state (VCCCP). AuNRs also provoked the decreasing in ROS production in the presence or absence of Ca2+ in addition to a delay on mitochondrial swelling. However, AuNRs caused the mitochondrial potential dissipation even in the presence os cyclosporin A (CsA), and at the highest concentration of gold (100 µM), AuNRs induced a disorder on mitochondrial crests and the intermembrane separation. These results indicate that BSA-adsorbed AuNRs may possibly interact with electron chain complex and interrupt the electron flow causing mitochondrial damages independent on the presence o Ca2+. This study provides new evidences of BSAadsorbed AuNRs effects on mitochondrial bioenergetics.