Interactions of light-sensitive drugs and materials with Cerenkov radiation-emitting radiopharmaceuticals generate cytotoxic reactive oxygen species (ROS) to inhibit localized and disseminated cancer progression, but the cell death mechanisms underlying this radionuclide stimulated dynamic therapy (RaST) remain elusive. Using ROS-regenerative nanophotosensitizers coated with a tumor-targeting transferrin-titanocene complex (TiO-TC-Tf) and radiolabeled 2-fluorodeoxyglucose (FDG), we found that adherent dying cells maintained metabolic activity with increased membrane permeabilization. Mechanistic assessment of these cells revealed that RaST activated the expression of RIPK-1 and RIPK-3, which mediate necroptosis cell death.
View Article and Find Full Text PDFRadionuclide-stimulated therapy (RaST), which is enhanced by Cherenkov radiation, has enabled deep tissue stimulation of UV photosensitizers, providing a new path for cancer treatment. Previous reports have shown UV-active titanium dioxide (TiO) nanoparticles (NPs) modified with transferrin inhibit tumour growth after orthogonal treatment with Cherenkov radiation-emitting radionuclides such as F-fluorodeoxyglucose (FDG). However, poor understanding of TiO NP parameters on reactive oxygen species (ROS) generation and particle distribution limits effective therapy.
View Article and Find Full Text PDFRapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for applications remains the Achilles' heel of nanomedicine, allowing only a small fraction of the materials to reach the intended target tissue. Although focusing on diseases that reside in the natural disposal organs for nanoparticles is a viable option, it limits the plurality of lesions that could benefit from nanomedical interventions. Here we designed a theranostic nanoplatform consisting of reactive oxygen (ROS)-generating titanium dioxide (TiO) NPs, coated with a tumor-targeting agent, transferrin (Tf), and radiolabeled with a radionuclide (Zr) for targeting bone marrow, imaging the distribution of the NPs, and stimulating ROS generation for cell killing.
View Article and Find Full Text PDFTitanium dioxide (TiO) nanoparticles have shown success as photosensitizers in the form of light-based cancer therapy called Cerenkov radiation induced therapy (CRIT). While TiO nanoparticles have been reported to be an effective therapeutic agent, there has been little work to control their functionalization and stability in aqueous suspension. In this work, the controlled coating of 25 nm diameter TiO nanoparticles with the glycoprotein transferrin (Tf) for application in CRIT was demonstrated using an electrospray system.
View Article and Find Full Text PDFAim: CaCO nanoparticles (nano-CaCO) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. We aim to develop a theranostic version of nano-CaCO to noninvasively monitor pH modulation and subsequent tumor response.
Materials & Methods: We synthesized ferromagnetic core coated with CaCO (magnetite CaCO).
Advanced automobile technology, developed infrastructure, and changing economic markets have resulted in increasing commute times. Traffic is a major source of harmful pollutants and consequently daily peak exposures tend to occur near roadways or while traveling on them. The objective of this study was to measure simultaneous real-time particulate matter (particle numbers, lung-deposited surface area, PM, particle number size distributions) and CO concentrations outside and in-cabin of an on-road car during regular commutes to and from work.
View Article and Find Full Text PDFComposite nanoparticles find application in catalysis, drug delivery, and energy storage and require increasingly fine control of their physical properties and composition. While composite nanoparticles have been widely synthesized and characterized, little work has systematically correlated the initial concentration of precursors and the final composition of flame synthesized composite nanoparticles. This relationship is explored in a diffusion flame aerosol reactor by coupling a scanning mobility particle sizer (SMPS) with an inductively coupled plasma optical emission spectrometer (ICP-OES).
View Article and Find Full Text PDFFront Plant Sci
September 2016
The use of agrochemical-nutrient fertilizers has come under scrutiny in recent years due to concerns that they damage the ecosystem and endanger public health. Nanotechnology offers many possible interventions to mitigate these risks by use of nanofertilizers, nanopesticides, and nanosensors; and concurrently increases profitability, yields, and sustainability within the agricultural industry. Aerosol based foliar delivery of nanoparticles may help to enhance nanoparticle uptake and reduce environmental impacts of chemical fertilizers conventionally applied through a soil route.
View Article and Find Full Text PDFAntacids are crucial in the treatment of gastro-esophageal reflux disease and peptic ulcers. Antacids based on the calcite phase of bulk calcium carbonate have been the standard for over fifty years. More recent research has shown that nanomaterial forms of such bulk materials often have improved properties.
View Article and Find Full Text PDFKinesin motors drive the long-distance anterograde transport of cellular components along microtubule tracks. Kinesin-dependent transport plays a critical role in neurogenesis and neuronal function due to the large distance separating the soma and nerve terminal. The fate of kinesin motors after delivery of their cargoes is unknown but has been postulated to involve degradation at the nerve terminal, recycling via retrograde motors, and/or recycling via diffusion.
View Article and Find Full Text PDFPrimary cilia regulate polarized protein trafficking in photoreceptors, which are dynamic and highly compartmentalized sensory neurons of retina. The ciliary protein Cep290 modulates cilia formation and is frequently mutated in syndromic and non-syndromic photoreceptor degeneration. However, the underlying mechanism of associated retinopathy is unclear.
View Article and Find Full Text PDFAdult bone marrow (BM) contains Sca-1+/Lin-/CD45- very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n= 11), 1 x 10(5) Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n= 13 [cell control group]), or 1 x 10(4) Sca-1+/Lin-/CD45- EGFP-labeled cells (n= 14 [VSEL-treated group]) at 48 hours after MI.
View Article and Find Full Text PDFLong-distance intracellular delivery is driven by kinesin and dynein motor proteins that ferry cargoes along microtubule tracks . Current models postulate that directional trafficking is governed by known biophysical properties of these motors-kinesins generally move to the plus ends of microtubules in the cell periphery, whereas cytoplasmic dynein moves to the minus ends in the cell center. However, these models are insufficient to explain how polarized protein trafficking to subcellular domains is accomplished.
View Article and Find Full Text PDFPharmacologic preconditioning by delta-opioid agonists occurs via activation of an adenosine triphosphate (ATP)-gated potassium channel (I(KATP)). Opening of mitochondrial I(KATP) confers pharmacologic preconditioning whereas opening the sarcolemmal I(KATP) shortens action potential duration and is proarrhythmic. This study investigated whether SNC-80, a selective delta-opioid agonist, is associated with development of ventricular arrhythmia due to activation of I(KATP).
View Article and Find Full Text PDFCalcium activated proteases (calpains) have been implicated in the processing of lens crystallins during lens maturation and cataract formation. Ubiquitous type calpain 2 and calpain 10 and lens specific Lp82 and Lp85 protein distribution were determined using immunohistochemistry and immunoblotting in embryonic and post-natal mouse eyes. Calpain 2 was first expressed late in embryonic development and localized to the lens epithelium and transition zone.
View Article and Find Full Text PDFBackground: Pax6 is a transcription factor that is required for induction, growth, and maintenance of the lens; however, few direct target genes of Pax6 are known.
Results: In this report, we describe the results of a cDNA microarray analysis of lens transcripts from transgenic mice over-expressing Pax6 in lens fibre cells in order to narrow the field of potential direct Pax6 target genes. This study revealed that the transcript levels were significantly altered for 508 of the 9700 genes analysed, including five genes encoding the cell adhesion molecules beta1-integrin, JAM1, L1 CAM, NCAM-140 and neogenin.
The susceptibility of Helicobacter pylori to disinfectants was compared to that of Escherichia coli. H. pylori is more resistant than E.
View Article and Find Full Text PDFPax6 is a transcription factor that regulates the development of the visual, olfactory, and central nervous systems, pituitary, and pancreas. Pax6 is required for induction, growth, and maintenance of the lens; however, few direct Pax6 target genes are known. This study was designed to identify batteries of differentially expressed genes in three related systems: 8-week old Pax6 heterozygous lenses, 8-week old Pax6 heterozygous eyes, and transgenic lenses overexpressing PAX6(5a), using high throughput cDNA microarrays containing about 9700 genes.
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