ABSTRACT
We present the new promising nanostructure- sandwich-like mesoporous silica nanoflakes synthesized on graphene oxide sheets core. In the first step biocompatibility of the nanoflakes with PEG and without functionalization in human fibroblast, melanoma and breast cancer cells was assessed. In order to define the cellular uptake in vitro and biodistribution in vivo the nanostructures were labelled with fluorescent dye. In the next step, the silica nanostructures were filled by the anticancer drug- methotrexate (MTX) and cytotoxicity of the complex in reference to MTX was evaluated. The WST-1 assay shows mild, but concentration dependent, cytotoxicity of the nanoflakes, most significant for the non-functionalized structures. PEG-modified silica nanoflakes didn't produce a disruption of cell membranes and lactate dehydrogenase (LDH) release. Cell imaging revealed efficient internalization of the silica nanoflakes in cells. Ex vivo organ imaging showed high accumulation of the nanostructures in lungs, bladder and gall bladder, whereas confocal imaging revealed wide nanoflake distribution in all tested tissues, especially at 1h and 4h post intravenous injection. Cytotoxicity of the nanoflake-MTX complex in reference to MTX showed similar cytotoxic potential against cancer cells. These findings may provide useful information for designing drug delivery systems, which may improve anticancer efficacy and decrease side effects.
Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Drug Delivery Systems , Methotrexate/administration & dosage , Nanostructures , Animals , Antimetabolites, Antineoplastic/pharmacokinetics , Antimetabolites, Antineoplastic/pharmacology , Breast Neoplasms/drug therapy , Cell Line, Tumor , Chemistry, Pharmaceutical/methods , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Injections, Intravenous , Male , Melanoma/drug therapy , Methotrexate/pharmacokinetics , Methotrexate/pharmacology , Mice , Mice, Inbred BALB C , Mice, Nude , Polyethylene Glycols/chemistry , Porosity , Silicon Dioxide/chemistry , Tissue DistributionABSTRACT
The effect of propylparaben (in final concentrations 0.4 ng/ml, 2.3 ng/ml and 4.6 ng/ml) on the energy metabolism of HepG2 hepatocytes, superoxide anion synthesis, apoptosis and necrosis is described. Propylparaben can be toxic to liver cells due to the increased production of superoxide anions, which can contribute to a reduced concentration of superoxide dismutase in vivo and impairment of the body's antioxidant mechanisms. Finally, a further reduction in the mitochondrial membrane potential and uncoupling of the respiratory chain resulting in a reduction in ATP concentration as a result of mitochondrial damage may lead to cell death by apoptosis.
