Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.</p

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

Design & development of collaborative workflow for lean production in a repair & overhaul industry

Aerospace fuel nozzles maintenance, repair and overhaul operation is a dynamic process as the workflow is unpredictable. Further detail checking and analyzing on defects are needed in order to determine the workflow. The traditional paper based of work in progress information had been implementing as to manage the nozzles production. However, paper based of work in progress information is inefficient in dealing with these unpredictable and complex workflows. There is a probability of entering or recording the error information when it is in paper based system. This wrong information will cause problem in production line as the results are inconsistent. Furthermore, this inaccurate result will lead to difficulty in tracking the nozzles. Excessive time is needed and wasted in indentifying and correcting the errors. Hence, an electronic based of work in progress system is apparently required as to overcome the shortcoming of the paper based tracking and also to enhance the efficiency of production line. This paper will describe the configurable and customizable work in progress tracking system as a mean to improve over the traditional paper based system

Quantification on the source/receptor relationship of primary pollutants and secondary aerosols by a Gaussian plume trajectory model: Part III-Asian dust-storm periods

Characteristics of pollutants at heights in the top of the Planetary Boundary Layer (PBL) are collected and used in a local-scale model. A subsidence mechanism is developed to quantify the concentration fraction from the top PBL to simulate PM concentration during Asian dust-storm (ADS) periods. The results show that using the data measured at a mountain station, which is very vulnerable to ADS, as the top boundary conditions for the air quality model can capture all the PM2.5 episodes due to local sources and ADS events, at a low-altitude urban station. The correlation coefficient (r(2)) of daily PM2.5-10 concentration has increased from 0.17 to 0.62 by incorporating the subsidence mechanism, and that of PM2.5 increases as well. The model results of nitrate, sulfate and ammonium aerosol in fine radii can be compared with observations. According to our analysis, five out of eight PM2.5 or PM10 episode days occurred on ADS days in the past 4 years (1999-2002). During ADS episodes in 2000, 12% of PM2.5 and 53% of PM2.5-10 were from ADS dust. In addition, two dry deposition algorithms are evaluated; the algorithm of Seinfeld and Pandis (Atmospheric Chemistry and Physics from Air Pollution to Climate Change, Wiley, New York, 1998, 1057pp.) is suggested in this case study. (C) 2003 Elsevier Ltd. All rights reserved