Nanoparticle dynamics in the presence and absence of a cellular uptake altering chemical

The far-reaching applications of nanoparticles (NPs) in drug delivery, medical imaging, diagnostics, and therapeutics have led to an increased potential for interfacing with a diverse range of biological environments. While metallic NPs such as copper NPs have been explored for their antimicrobial and catalytic properties, they have been shown to induce undesirable toxic effects. Nonetheless, biomodulators may be employed to control this cytotoxicity. Dynasore is a dynamin GTPase inhibitor that has been shown to rapidly and reversibly block clathrindependent endocytic traffic within minutes of application. Here, we demonstrate that Dynasore can chemically bio-modulate the toxic effects of copper nanoparticles (Cu NPs), but not through reducing Cu NP internalization. In fact, Dynasore seems to possess secondary effects that have been unreported to date. We propose and test three potential mechanisms of cytotoxicity modulation: 1) through changes in agglomeration pattern, 2) through potential quenching of reactive oxygen species (ROS), and 3) through Cu+2 ion chelation. These results have far-reaching implications for understanding the complex interactions that occur at the interface of NPs in biological environments, especially during mechanistic chemical modification strategies

Fair Value Hierarchy Measures: Post-Implementation Evidence on IFRS 7

Using a balance sheet valuation model, this study examines if information on the fair value hierarchy of on-balance sheet financial assets and financial liabilities are incorporated in the market’s valuation of companies’ equities in Singapore. The results of the study show significant associations between as-reported Level 1 and Level 2 fair value measures of financial assets and market values. However, the results are not significant for Level 3 fair value measures of financial assets and each of the three levels of fair value measures of financial liabilities. The results also show that returns are more positively associated with as-reported gains and losses from Level 1 and Level 2 fair value measures than those from Level 3 fair value measures. Overall, the evidence suggests that information on the fair value hierarchy of IFRS 7 Financial Instruments: Disclosures are used by market participants in their pricing decisions. The market however appears to place greater weights on fair value changes taken to the income statement than those taken to OCI, notwithstanding the level of the fair value measure. While the fixation with income statement measures remains a puzzle, the results are consistent with prior studies that show that investors largely ignore OCI in their pricing of shares

A filter-free blood-brain barrier model to quantitatively study transendothelial delivery of nanoparticles by fluorescence spectroscopy

The delivery of therapeutics to the brain is greatly hampered by the blood-brain barrier (BBB). The use of nanoparticles that can cross the BBB via the process of receptor-mediated transcytosis at blood-brain barrier endothelial cells seems a promising strategy to transport therapeutics into the brain. To screen for suitable nanocarriers, and to study the process of transcytosis, a cultured polarized monolayer of brain microvascular endothelial cells on an extracellular matrix-coated porous membrane filter is widely used as an in vitro BBB model. However, due to the adhesion of numerous types of nanoparticles to the membrane filter and within the filter pores, such a model is unsuitable for the quantification of transendothelial delivery of nanoparticles. Hence, there is a pressing need for a filter-free in vitro BBB model. Ideally, the model is inexpensive and easy to use, in order to allow for its wide use in nanomedicine and biology laboratories around the world. Here, we developed a filter-free in vitro BBB model that consists of a collagen gel covered with a monolayer of brain microvascular endothelial (hCMEC/D3) cells. The paracellular leakage of differently sized dextrans and the transcellular transport of LDL were measured to demonstrate the validity of the filter-free model. Finally, the transendothelial delivery of fluorescently-labelled PEG-P(CL-g-TMC) polymersomes that were functionalized with GM1-targeting peptides was assessed by fluorescence spectroscopy measurement of the luminal, cellular, and abluminal parts of the filter-free BBB model. Our data confirm the effectiveness of the G23 peptide to mediate transport of polymersomes across the BBB and the suitability of this filter-free in vitro model for quantification of nanoparticle transcytosis