Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application,Spatial Distribution,and Dosimetry

Targeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X‐ray (two modes) and fluorescence imaging (three modes) techniques for time‐resolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X‐ray) and/or (nano)particles (X‐ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator‐assisted aerosol inhalation. It is demonstrated that in vivo propagation‐based phase‐contrast X‐ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue‐cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and novel‐designed NM for targeting and efficacy.     

Transport of surface-modified nanoparticles through cell monolayers

We synthesized three peptides, a D-polyarginyl peptide (r8(FITC)), a Tat peptide (Tat(FITC)), and a control peptide (Cp(FITC)) and attached each to amino-CLIO, a nanoparticle 30 nm in diameter. We then examined the effective permeability, Peff, of all six materials through CaCo-2 monolayers. The transport of peptide-nanoparticles was characterized by a lag phase (0-8 h) and a steady-state phase (9-27 h). The steady-state Peff values for peptides were in the order r8(FITC)>Tat(FITC)=Cp(FITC). When r8(FITC) and Tat(FITC) peptides were attached to the nanoparticle, they conferred their propensity to traverse cell monolayers onto the nanoparticle, whereas Cp(FITC) did not. Thus, when the r8(FITC) peptide was attached to the amino-CLIO nanoparticle, the resulting peptide-nanoparticle had a Peff similar to that of this poly-D-arginyl peptide alone. The Peff of r8(FITC)-CLIO (MW approximately 1000 kDa) was similar to that of mannitol (MW=182 Da), a poorly transported reference substance, with a far lower molecular weight. These results are the first to indicate that the modification of nanoparticles by attachment of membrane-translocating sequence-based peptides can alter nanoparticle transport through monolayers. This suggests that the surface modification of nanoparticles might be a general strategy for enhancing the permeability of drugs and that high-permeability nanoparticle-based therapeutics can be useful in selected pharmaceutical applications.     

Non-isothermal NO x storage/release over manganese based traps: mechanistic considerations

Topics in Catalysis - The NO storage properties of MnO x /support materials (5–50 wt% MnO x loading) was experimentally investigated in the presence of O2 and H2O between 50 and...     

The sale of council housing in the inter‐war period

This paper examines the sale of council housing between the wars and discusses the implications which findings on early council house sales have for an understanding of the owner occupied market at a critical period of its development. The paper first looks at the sales policy in England and Scotland and then focuses on Edinburgh, where, because of the political constitution of the Corporation, sales were actively encouraged. There then follows an analysis of the class structure of tenants and owners on the main 1919 Act estates in the city. The reluctance of sitting tenants to purchase council houses, together with information on their alternative choices, supports the argument that the move into owner occupation at this time was not the result of an innate desire to own but was a rational decision. What was important were the relative costs of renting and buying, and the attractiveness and availability of owner occupied housing compared with housing in other tenures.     

Social comparison and adjustment to breast cancer: An experimental examination of upward affiliation and downward evaluation.

In a study designed to evaluate the divergence of social comparison activities under health threat, breast cancer patients (n?=?94) were assigned randomly to listen to an audiotaped interview in which the target's psychological adjustment and disease prognosis were manipulated to reflect good, poor, and unspecified psychological and physical health status. Results supported hypotheses regarding downward self-evaluative and upward affiliative comparison activity, as well as predictions regarding the influences of comparison dimension. With regard to desire for affiliation, participants demonstrated a greater desire for information and emotional support from the well-adjusted target than from the poorly adjusted target. Self-evaluation of adjustment and prognosis varied as a function of target characteristics, although a pervasive tendency toward downward comparison in self-evaluation also was noted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polymer-filler derived Mo2C ceramics

Manufacturing, microstructure and properties of novel reaction bonded Mo₂C materials derived from polymer/reactive filler mixtures were investigated. Mo powder was used as a filler to react with carbon bearing decomposition products of poly(methyl- and phenysiloxanes) during pyrolysis in nitrogen atmosphere. Microcrystalline composites with the filler reaction products Mo₃C, Mo₃Si, Mo₅Si₃ embedded in a silicon oxycarbide glass matrix could be formed with complex geometry owing to near net shape polymer/ceramic conversion. Depending on the precursor composition and pyrolysis conditions, ceramic hard materials with a density up to 97% theoretical density, a hardness of 10 GPa, a Young’s Modulus of 250 GPa, a fracture toughness of 5 MPam^1/2 and a flexural strength of 330 MPa were obtained.     

Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

The purine nucleotide adenosine triphosphate (ATP) is known for its fundamental role in cellular bioenergetics. However, in the last decades, different works have described emerging functions for ATP, such as that of a danger signaling molecule acting in the extracellular space on both tumor and stromal compartments. Beside its role in immune cell signaling, several studies have shown that high concentrations of extracellular ATP can directly or indirectly act on cancer cells. Accordingly, it has been reported that purinergic receptors are widely expressed in tumor cells. However, their expression pattern is often associated with contradictory cellular outcomes. In this work, we first investigated gene expression profiles through “RNA-Sequencing” (RNA Seq) technology in four colorectal cancer (CRC) cell lines (HT29, LS513, LS174T, HCT116). Our results demonstrate that CRC cells mostly express the A2B, P2X4, P2Y1, P2Y2 and P2Y11 purinergic receptors. Among these, the P2Y1 and P2Y2 coding genes are markedly overexpressed in all CRC cells compared to the HCEC-1CT normal-like colonic cells. We then explored the cellular outcomes induced by extracellular ATP and adenosine. Our results show that in terms of cell death induction extracellular ATP is consistently more active than adenosine against CRC, while neither compound affected normal-like colonic cell survival. Intriguingly, while for the P2Y2 receptor pharmacological inhibition completely abolished the rise in cytoplasmic Ca²⁺ observed after ATP exposure in all CRC cell lines, Ca²⁺ mobilization only impacted the cellular outcome for HT29. In contrast, non-selective phosphodiesterase inhibition completely abolished the effects of extracellular ATP on CRC cells, suggesting that cAMP and/or cGMP levels might determine cellular outcome. Altogether, our study provides novel insights into the characterization of purinergic signaling in CRC.     

Compact High-Velocity Atmospheric Pressure Dielectric Barrier Plasma Jet in Ambient Air

In this paper,a non-thermal atmospheric pressure plasma jet at high streaming velocity operating with ambient air is highlighted.In the present technological approach,the employment of air poses a significant challenge.The high oxygen concentration in air results in a reduced concentration of reactive species in combination with a short species lifetime.The plasma jet assembly presented here contains a special dielectric barrier with a high secondary emission coefficient.In this way,the electron density and in turn the density of reactive species is increased.In addition,the plasma jet assembly is equipped with a short electrode.This leads to a higher voltage across the discharge gap and in turn to an increased density of reactive plasma species.The plasma jet is formed within and emitted by a small conical nozzle.A high-speed gas flow with gas velocity of 340 m/s was achieved at the end of the nozzle.In the jet the concentration of toxic and unwanted neutral plasma species like O_3 or NO_x is significantly reduced because of the shorter residence time within the plasma.The range of short-lived active plasma species is in turn considerably enhanced.The jet efficiency and action range measured through the oxidation of a test surface were determined by measuring the increase of surface tension of a polypropylene substrate via contact angle measurements after plasma treatment.Numerical modeling of the plasma plume indicates that oxygen atoms are in fact the main active species in the plasma plume.