Matrix metalloproteases inhibition and biocompatibility of gold and platinum nanoparticles

Abstract

Matrix metalloprotease (MMP) inhibitors improve the longevity of dental adhesives/tooth bonds; however, biocompatibility is required for their clinical use. This study evaluated the inhibition of MMPs and toxicity of two gold (AuNPs) and platinum nanoparticles (PtNPs) as possible compounds for use in dental adhesives. The MMP assay for studying the interaction of MMPs and nanoparticles (NPs) was evaluated by an MMP assay kit and gelatin zymography. Cultured L929 fibroblast cells or RAW264 macrophages were exposed to NPs. The cellular responses to NPs were examined using cytotoxic (cell viability) and genotoxic assays (comet assay), and transmission electron microscopic (TEM) analysis. The mechanical properties (elastic modulus) of the experimental resin loaded with NPs were examined using thermomechanical analysis. All NPs inhibited MMP activity at relatively low concentrations. The NPs inhibit MMPs by chelating with the Zn(2+) bound in the active sites of MMPs. No cytotoxic and genotoxic effects were found in AuNPs, whereas the PtNPs possessed both adverse effects. In TEM analysis, the NPs were localized mainly in lysosomes without penetration into nuclei. The mechanical properties of the resins increased when AuNPs were added in resins, but not by PtNPs. AuNPs are attractive candidates to inhibit MMPs and improve the mechanical properties of resins without cytotoxic/genotoxic effects to cells, and therefore should be suitable for applications in adhesive resin systems.

Platinum corrosion products from electrode contacts of human cochlear implants induce cell death in cell culture models

“…Only at 100 μg/ml Pt-NP concentration cell metabolism and mitochondrial activity were reduced. Our results were in line with previous in vitro studies exposing murine L929 fibroblasts, several human cell lines such as RAW264, A549, HaCaT, IMR90 and U251 to Pt-NP with a primary size less than 10 nm: no or only moderate cell death induction were observed [ 35 – 38 ]. Significant toxicity was only found in IMR90, U251 L929 and RAW264 cells following exposure to 80–100 μg/ml Pt-NP [ 35 , 38 – 39 ].…”

“…In addition to Pt ions and its complexes traces of solid Pt particles were also found in the spiral ligament, connective tissue around the electrode, macrophages and even in the middle ear [ 8 , 14 , 32 – 34 ]. In vitro cytotoxic and genotoxic effects of Pt nanoparticles with average size below 10 nm have not been demonstrated at concentrations below 80–100 μg/ml in several cell lines thus far [ 35 – 38 ]. However, it has also been reported that–depending on the cell type and organism–Pt-NP induced oxidative stress, DNA damage, inflammation or other negative biological effects in a concentration-depending manner [ 39 – 44 ].…”

A Comprehensive Review on the Synthesis, Characterization, and Biomedical Application of Platinum Nanoparticles

“…Larger sizes of particles showed decreasing cell metabolism, but there was no significant effect on cell viability or migration, whereas smaller NPs exhibited more deleterious effects on DNA stability, and these triggered caspases [213]. Fibroblast cells L929 or macrophages RAW264 treated with PtNPs exhibited loss of cell viability and DNA damage, and PtNPs also inhibited matrix metalloprotease (MMP) activity [214]. Biologically synthesized PtNPs using pomegranate extract showed cytotoxic effects against MCF-7 cell line by decreasing cell viability and increasing apoptosis and DNA damage [100].…”

Addressing Nanomaterial Immunosafety by Evaluating Innate Immunity across Living Species

“…[131,132] During an inflammatory reaction, innate immune cells produce matrix metalloproteinases (MMP), which are factors involved in the degradation and remodeling of the extracellular matrix during wound healing. Recently it has been reported that different NM (Ag, Au, Zn, and carbon-based NP) can regulate the synthesis of some MMP, [133,134] although the variability of study models and of NM used does not yet allow full understanding. Overall, the possibility of using NM to modulate/control the immune cell activation and their ROS and MMP production opens promising perspectives for new therapeutic approaches.…”