Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus

Whether mucus layers lining entrance points into the body, including the lung airways, provide protection against the penetration of engineered nanoparticles remains poorly understood. We measured the diffusion coefficients of hundreds of individual nanoparticles of three different metal oxides (nMeOs) and two types of single-walled carbon nanotubes (SWCNTs) in undiluted human mucus. We found that the vast majority of these nanoparticles are efficiently trapped in human mucus and, further, that the mechanism of trapping is adhesive interactions as opposed to steric obstruction. However, a small fraction of zinc oxide (ZnO) nanoparticles moved at rates fast enough to penetrate airway mucus layers. We conclude that human mucus layers probably provide considerable protection for mucosal tissues from the penetration of most nMeOs and SWCNTs, and suggest that further investigation of the potential health risks of exposure to ZnO nanoparticles is warranted.     

In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes

The present study compared the photothermal anticancer activity of near-infrared (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower NIR-absorbing capacity, suspension of polyvinylpyrrolidone-coated graphene sheets exposed to NIR radiation (808 nm, 2 W/cm(2)) generated more heat than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same conditions. Accordingly, graphene nanoparticles performed significantly better than CNT in inducing photothermal death of U251 human glioma cells in vitro. The superior photothermal sensitivity of graphene sheets could be largely explained by their better dispersivity, which has been supported by a simple calculation taking into account thermodynamic, optical and geometrical properties of the two type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal killing of cancer cells apparently involved oxidative stress and mitochondrial membrane depolarization resulting in mixed apoptotic and necrotic cell death characterized by caspase activation/DNA fragmentation and cell membrane damage, respectively.     

Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene

Using the rat glioma cell line C6 and the human glioma cell line U251, we demonstrate the multiple mechanisms underlying the in vitro anticancer effects of the C(60) fullerene water suspension (nano-C(60) or nC(60)) produced by solvent exchange method. Nano-C(60) in a dose-dependent manner reduced the tumor cell numbers after 24 h of incubation. The observed antiglioma action of nC(60) at high concentration (1 microg/ml) was due to a reactive oxygen species-mediated necrotic cell damage that was partly dependent on oxidative stress-induced activation of extracellular signal-regulated kinase (ERK). On the other hand, low-dose nC(60) (0.25 microg/ml) did not induce either necrotic or apoptotic cell death, but caused oxidative stress/ERK-independent cell cycle block in G(2)/M phase and subsequent inhibition of tumor cell proliferation. Treatment with either high-dose or low-dose nC(60) caused the appearance of acidified intracytoplasmic vesicles indicative of autophagy, but only the antiglioma effect of low-dose nC(60) was significantly attenuated by inhibiting autophagy with bafilomycin A1. Importantly, primary rat astrocytes were less sensitive than their transformed counterparts to a cytostatic action of low-dose nC(60). These data provide grounds for further development of nC(60) as an anticancer agent.     

Proliferation and bone-related gene expression of osteoblasts grown on hydroxyapatite ceramics sintered at different temperature

Human osteoblast-like cells SaOS-2 (ATCC HTB85) were seeded onto three kinds of hydroxyapatite (HA) ceramics sintered at different temperature (1200 degrees C, 1000 degrees C and 800 degrees C). Scanning electron microscopy (SEM) was conducted to detect the surface microstructure. Cells were cultured on these substrates for 6 and 12 days and cell proliferation rate and mRNA expression for osteocalcin, osteonectin, type I collagen and alkaline phosphatase and protein production for osteocalcin, bone sialoprotein and osteonectin were detected with quantitative in situ hybridization and immunocytochemistry techniques. SEM revealed that crystal particle size was affected by sintering temperature. Result showed that cell proliferation rate on HA ceramics sintered at 1200 degrees C was the highest. Osteonectin and type I collagen mRNA expression was not altered by sintering temperature. After 12 days in culture, bone sialoprotein, osteocalcin and osteonectin proteins levels were significantly (p<0.05) higher when SaOS-2 cells were cultured on HA sintered at 1200 degrees C, compared to the other two surfaces, suggesting that HA sintered at high temperature may be a better candidate for in vivo implantation. This result provides valuable information concerning the clinic application of HA ceramics sintered at different temperature.     

Acquired pMHC I Complexes Greatly Enhance CD4~+ Th Cell’s Stimulatory Effect on CD8~+ T Cell-Mediated Diabetes in Transgenic RIP-mOVA Mice

CD4+ helper T (Th) cells play pivotal roles in induction of CD8+ CTL immunity. However, the mechanism of CD4+ T cell help delivery to CD8+ T cells in vivo is still elusive. In this study, we used ovalbumin (OVA)-pulsed dendritic cells (DCOVA) to activate OT-II mouse CD4+ T cells, and then studied the help effect of these CD4+ T cells on CD8+ cytotoxic T lymphocyte (CTL) responses. We also examined CTL mediated islet β cell destruction which led to diabetes in wild-type C57BL/6 mice and transgenic rat insuli...