Intercomparison of radiosensitization induced by gold and iron oxide nanoparticles in human glioblastoma cells irradiated by 6 MV photons.

In this work, an intercomparison of sensitization effects produced by gold (GNP) and dextran-coated iron oxide (SPION-DX) nanoparticles in M059J and U87 human glioblastoma cells was performed using 6 MV-photons. Three variables were mapped: the nanoparticle material, treatment concentration, and cell radiosensitivity. For U87, GNP treatments resulted in high sensitization enhancement ratios (SER[Formula: see text] up to 2.04). More modest effects were induced by SPION-DX, but still significant reductions in survival were achieved (maximum SER[Formula: see text] ). For the radiosensitive M059J, sensitization by both NPs was poor. SER[Formula: see text] increased with the degree of elemental uptake in the cells, but not necessarily with treatment concentration. For GNP, where exposure concentration and elemental uptake were found to be proportional, SER[Formula: see text] increased linearly with concentration in both cell lines. For SPION-DX, saturation of sensitization enhancement and metal uptake occurred at high exposures. Fold change in the [Formula: see text] ratios extracted from survival curves are reduced by the presence of SPION-DX but strongly increased by GNPs , suggesting that sensitization by GNPs occurs mainly via promotion of lethal damage, while for SPION-DX repairable damage dominates. The NPs were more effective in eliminating the radioresistant glioblastoma cells, an interesting finding, as resistant cells are key targets to improve treatment outcome.

Nanoscale Structural Characterization and Impact on Long-term memory of Amyloid-ß42 Oligomeric forms in Zebrafish.

The contribution of amyloid-ß (Aß) soluble forms to Alzheimer's Disease (AD) is undergoing revision and the characterization of monomeric, oligomeric and protofibrillar Aß forms used in vivo to model AD is a critical step to ensure data interpretation. Atomic force microscopy (AFM) was used to characterize the nanoscale morphology of different Aß42 forms also used for cerebroventricular injection (cvi) in young (6mo) and aged (36mo) adult zebrafish behavioral and cognitive tests. On the AFM, monomeric solution deposited onto mica resulted mostly in thin filamentous structures and shorter monomeric agglomerates with heights around or below 1.5 nm, as expected for single Aß42. The oligomeric form was dominated by particles with globular morphology and a few short aggregates around 1 nm high and 8-12 nm long. The protofibrillar form had micrometer-long twisted fibrils of varying diameters (4.5-10 nm) and large entangled clusters with sizes of up to several tens of micrometers. On the Open Tank used to test exploratory parameters, no differences were observed between injected animals and their age-matched controls, except for a reduced distance travelled by aged individuals that received the Aß42 oligomeric form. Long-term memory (LTM) for the inhibitory avoidance task was not influenced by monomers cvi, whilst oligomeric and fibrillar Aß42 hindered LTM formation in young and aged groups. Our findings support current views of deleterious effects of Aß42 soluble forms on cognition and ensures that preparations were structurally unique and within expected morphologies and dimensions.

Iron Oxide Nanoparticles Labeled with an Excited-State Intramolecular Proton Transfer Dye.

Excited-state intramolecular proton transfer (ESIPT) is a particularly well known reaction that has been very little studied in magnetic environments. In this work, we report on the photophysical behavior of a known ESIPT dye of the benzothiazole class, when in solution with uncoated superparamagnetic iron oxide nanoparticles, and when grafted to silica-coated iron oxide nanoparticles. Uncoated iron oxide nanoparticles promoted the fluorescence quenching of the ESIPT dye, resulting from collisions during the lifetime of the excited state. The assembly of iron oxide nanoparticles with a shell of silica provided recovery of the ESIPT emission, due to the isolation promoted by the silica shell. The silica network gives protection against the fluorescence quenching of the dye, allowing the nanoparticles to act as a bimodal (optical and magnetic) imaging contrast agent with a large Stokes shift.