Would Colloidal Gold Nanocarriers Present An Effective Diagnosis Or Treatment For Ischemic Stroke?

INTRODUCTION: This study was conducted to evaluate OX26-PEG-coated gold nanoparticles (GNPs) (OX26@GNPs) as a novel targeted nanoparticulate system on cell survival after ischemic stroke. MATERIALS AND METHODS: Dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM) were performed to characterize the OX26@GNPs. The effect of OX26@GNPs on infarct volume, neuronal loss, and necroptosis was evaluated 24 h after reperfusion using 2, 3,5-Triphenyltetrazolium chloride (TTC) staining, Nissl staining and Western blot assay, respectively. RESULTS: Conjugation of OX26-PEG to the surface of the 25 nm colloidal gold particles increased their size to 32±2 nm, while a zeta potential change of -40.4 to 3.40 mV remarkably increased the stability of the nanoparticles. Most importantly, OX26@GNPs significantly increased the infarcted brain tissue, while bare GNPs and PEGylated GNPs had no effect on the infarct volume. However, our results indicated an extension of necroptotic cell death, followed by cell membrane damage. CONCLUSION: Collectively, our results showed that the presently formulated OX26@GNPs are not suitable nanocarriers nor contrast agents under oxidative stress for the diagnosis and treatment of ischemic stroke. Moreover, our findings suggest that the cytotoxicity of GNPs in the brain is significantly associated with their surface charge.

Effects of long-term exposure to colloidal gold nanorods on freshwater microalgae.

Gold nanorods have shown to pose adverse effects to biota. Whether these effects may be potentiated through prolonged exposure has been rarely studied. Therefore, this work aimed at evaluating the effects of long-term exposure to sublethal levels of cetyltrimethylammonium bromide (CTAB) coated gold nanorods (Au-NR) on two freshwater microalgae: Chlorella vulgaris and Raphidocelis subcapitata. These algae were exposed to several concentrations of Au-NR for 72 h and, afterwards, to the corresponding EC5,72h, for growth, during 16 days. The sensitivity of the two algae to Au-NR was assessed at days 0, 4, 8, 12 and 16 (D0, D4, D8, D12 and D16, respectively) after a 72-h exposure to several concentrations of Au-NR. At the end of the assays, effects on yield and population growth rate were evaluated. Raphidocelis subcapitata was slightly more sensitive to Au-NR than C. vulgaris: EC50,72h,D0 for yield were 48.1 (35.3-60.9) and 70.5 (52.4-88.6) µg/L Au-NR, respectively while for population growth rate were above the highest tested concentrations (53 and 90 µg/L, respectively). For R. subcapitata the long-term exposure to Au-NR increased its sensitivity to this type of nanostructures. For C. vulgaris, a decrease on the effects caused by Au-NR occurred over time, with no significant effects being observed for yield or population growth rate at D12 and D16. The capping agent CTAB caused reductions in yield above 30% (D0) for both algae at the concentration matching the one at the highest Au-NR tested concentration. When exposed to CTAB, the highest inhibition values were 69% (D4) and 21.3% (D8) for R. subcapitata, and 64% (D12) and 21% (D16) to C. vulgaris, for yield and population growth rate, respectively. These results suggested long-term exposures should be included in ecological risk assessments since short-term standard toxicity may either under- or overestimate the risk posed by Au-NR.

Colloidal Gold Nanoparticles Induce Changes in Cellular and Subcellular Morphology.

Exposure of cells to colloidal nanoparticles (NPs) can have concentration-dependent harmful effects. Mostly, such effects are monitored with biochemical assays or probes from molecular biology, i.e., viability assays, gene expression profiles, etc., neglecting that the presence of NPs can also drastically affect cellular morphology. In the case of polymer-coated Au NPs, we demonstrate that upon NP internalization, cells undergo lysosomal swelling, alterations in mitochondrial morphology, disturbances in actin and tubulin cytoskeleton and associated signaling, and reduction of focal adhesion contact area and number of filopodia. Appropriate imaging and data treatment techniques allow for quantitative analyses of these concentration-dependent changes. Abnormalities in morphology occur at similar (or even lower) NP concentrations as the onset of reduced cellular viability. Cellular morphology is thus an important quantitative indicator to verify harmful effects of NPs to cells, without requiring biochemical assays, but relying on appropriate staining and imaging techniques.

Magnetic gold nanoparticle-mediated small interference RNA silencing Bag-1 gene for colon cancer therapy.

Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 was very slightly expressed in normal tissues, but often highly expressed in many tumor tissues, particularly in colon cancer, which can promote metastasis, poor prognosis and anti-apoptotic function of colon cancer. We prepared and evaluated magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex, a gene therapy system, which can transfect cells efficiently, for both therapeutic effect and safety in vitro mainly by electrophoretic mobility shift assays, flow cytometric analyses, cell viability assays, western blot analyses and RT-PCR (real-time) assays. Magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex was successfully transfected into LoVo colon cancer cells and the exogenous gene was expressed in the cells. Flow cytometric results showed apoptosis rate was significantly increased. In MTT assays, magnetic gold nanoparticles revealed lower cytotoxicity than Lipofectamine 2000 transfection reagents (P<0.05). Both in western blot analyses and RT-PCR assays, magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex transfected cells demonstrated expression of Bag-1 mRNA (P<0.05) and protein (P<0.05) was decreased. In further study, c-myc and ß-catenin which are main molecules of Wnt/ß­catenin pathway were decreased when Bag-1 were silenced in nanoparticle plasmid complex transfected LoVo cells. These results suggest that magnetic gold nanoparticle mediated siRNA silencing Bag-1 is an effective gene therapy method for colon cancer.

Colloidal metallic gold is not bio-inert.

Metallic gold (Au degrees ) is a likely biotransformation product of monovalent gold, Au(I) whenever it is dissociated from in vivo ligands, Au degrees being formed either by bioreduction or by spontaneous dismutation (with co-production of trivalent gold). This review discusses the preparation and some biologically relevant properties of colloidal metallic gold (CMG) in its nano-particulate form. Tyndall's purple, a well characterised preparation of CMG, shows potent anti-arthritic activity in rats, approximately 10(3) times that of sodium aurothiomalate (Myocrysin). Even more remarkable is its broader spectrum of action in rats compared to this classic DMARD.

Mammalian sensitivity to elemental gold (Au degrees).

There is increasing documentation of allergic contact dermatitis and other effects from gold jewelry, gold dental restorations, and gold implants. These effects were especially pronounced among females wearing body-piercing gold objects. One estimate of the prevalence of gold allergy worldwide is 13%, as judged by patch tests with monovalent organogold salts. Eczema of the head and neck was the most common response of individuals hypersensitive to gold, and sensitivity can last for at least several years. Ingestion of beverages containing flake gold can result in allergic-type reactions similar to those seen in gold-allergic individuals exposed to gold through dermal contact and other routes. Studies with small laboratory mammals and injected doses of colloidal gold showed increased body temperatures, accumulations in reticular cells, and dose enhancement in tumor therapy; gold implants were associated with tissue injuries. It is proposed that Au degrees toxicity to mammals is associated, in part, with formation of the more reactive Au+ and Au3+ species.