Microfluidic three-dimensional biomimetic tumor model for studying breast cancer cell migration and invasion in the presence of interstitial flow

Cell migration and invasion are critical steps in cancer metastasis, which are the major cause of death in cancer patients. Tumor-associated macrophages(TAMs) and interstitial flow(IF) are two important biochemical and biomechanical cues in tumor microenvironment, play essential roles in tumor progression. However, their combined effects on tumor cell migration and invasion as well as molecular mechanism remains largely unknown. In this work, we developed a microfluidic-based 3 D breast cancer model by co-culturing tumor aggregates, macrophages, monocytes and endothelial cells within 3 D extracellular matrix in the presence of IF to study tumor cell migration and invasion. On the established platform, we can precisely control the parameters related to tumor microenvironment and observe cellular responses and interactions in real-time. When co-culture of U937 with human umbilical vein endothelial cells(HUVECs) or MDA-MB-231 cells and tri-culture of U937 with HUVECs and MDA-MB-231 cells, we found that mesenchymal-like MDA-MB-231 aggregates activated the monocytes to TAM-like phenotype macrophages. MDA-MB-231 cells and IF simultaneously enhanced the macrophages activation by the stimulation of colony-stimulating factor 1(CSF-1). The activated macrophages and IF further promoted vascular sprouting via vascular endothelial growth factor(VEGFα) signal and tumor cell invasion. This is the first attempt to study the interaction between macrophages and breast cancer cells under IF condition. Taken together, our results provide a new insight to reveal the important physiological and pathological processes of macrophages-tumor communication. Moreover, our established platform with a more mimetic 3 D breast cancer model has the potential for drug screening with more accurate results.     

Construction of peptide-vehicles,bioconjugates having modules for cancer cell surface capture and cell-penetrating peptide with anticancer agents

Recently molecular targeting therapy has been applied to cancer chemotherapy, although in some cases side-effects are not negligible. Based on our bio-detection concept, that is, protein–protein interaction can be mimicked by using peptides, a novel cell-targeting concept designated peptide-vehicle has been proposed, which has conjugates consisting of the cancer cell recognition and cell penetrating peptides with anticancer drugs. The cancer cell surface protein can be captured by a cyclotide, containing protease resistant d-cystine. A library of cell penetrating peptides has been prepared and conjugated to the cyclotide. Anticancer molecules were recovered after clinical use, which were pooled, purified, and derivatized for loading into the vehicle. The present Letter describes construction of peptide-vehicles, bioconjugates focusing on more efficiency and cancer cell selective delivery for anticancer drugs.     

Optimization of the fractional precipitation of paclitaxel from a Taxus chinensis cell culture using response surface methodology and its isolation by consecutive high‐speed countercurrent chromatography

A consecutive preparation method for the isolation and purification of paclitaxel from the Taxus Chinensis cell culture was developed in this study. The process involved alkaline Al₂O₃ chromatography, fractional precipitation, and high‐speed countercurrent chromatography. The original cell culture materials were first extracted with methanol using ultrasound‐assisted extraction, and then the extract (the content of paclitaxel is 1.5%) was separated by alkaline Al₂O₃ column chromatography. Subsequently, fractional precipitation was used to obtain paclitaxel. In particular, response surface methodology was used to optimize the factors of fractional precipitation (methanol concentration, material‐to‐solvent ratio, and precipitating time were optimized as 48.14%, 8.85 mg/mL, and 48.71 h, respectively) and the yield of fractional precipitation product was 30.64 ± 0.60 mg (the content of paclitaxel is 89.3%, 27.37 ± 0.54 mg) from a 100 mg fraction by Al₂O₃ column separation (the content of paclitaxel is 32.4%). Then, the product was used for further isolation by high‐speed countercurrent chromatography. About 1.00 g paclitaxel (200 ± 2 mg in each loading) with a purity up to 99.61% was isolated from 1.25 g of fractional precipitation product with a solvent system of n‐hexane/ethyl acetate/methanol/water (1.2:1.8:1.5:1.5, v/v/v/v) in one run of five consecutive sample loadings without exchanging a new solvent system.     

Synthesis of a novel oil‐absorption resin and optimization of its performance parameters using response surface design

A novel porous oil absorbing resin with the main monomers of stearyl methacrylate and isooctyl methacrylate was synthesized using suspension polymerization. The synthesis experiments were conducted using the response surface design method. And the influences of initiator concentration, cross‐linker concentration, and dispersant concentration were investigated. Through analyzing the second‐order polynomial mathematical models and the corresponding data, the mutual effects between these factors on the oil‐absorption performance were obtained. The response surface was used to analyze the oil (gasoline, diesel, and kerosene) absorption performance in the pure oil samples and oily water samples, respectively. The content of initiator and cross‐linker exhibited a necessary effect on the absorption of gasoline and kerosene. Moreover, the two most significant factors for diesel are the amount of initiator and dispersant. The experimental results showed that the oil‐absorbing resin synthesized under the optimized condition could achieve better oil‐absorption rate on all three oils. The absorption rates of gasoline, diesel, and kerosene are 10.14, 10.73, and 11.69 g/g, respectively, which the deoiling rate can reach closed 100% in the water sample containing gasoline and kerosene.     

Effects of oxygen plasma treatment on the surface of bisphenol A polycarbonate: a study using SIMS,principal component analysis,ellipsometry, XPS and AFM nanoindentation

The effects of oxygen plasma treatment and the subsequent air exposure on the surface composition and properties of bisphenol A polycarbonate (BPA‐PC) were analysed by X‐ray photoelectron spectroscopy (XPS), ellipsometry, static time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) with principal component analysis (PCA) and nanoindentation using an atomic force microscope (AFM). PCA showed systematic changes in the film chemistry after short treatment times (0.1 s), with the main sites of attack being the carbonate and aromatic ring structure. On the basis of this multitechnique analysis, it was unambiguously determined that extended oxygen plasma treatment times resulted in the formation of low‐molecular‐weight material (LMWM) within the first 50 nm on the surface, and not in a cross‐linked skin as has been proposed by other researchers. The study shows that controlled surface modification of BPA‐PC polymers is possible, allowing surface oxygen incorporation without degradation of the polymer structure. This result is relevant for improved adhesion of coatings applied to BPA‐PC polymers. Copyright © 2006 John Wiley & Sons, Ltd.     

Determination of As(III) by anodic stripping voltammetry using a lateral gold electrode: experimental conditions, electron transfer and monitoring of electrode surface

The aim of this work is to evaluate the efficiency of the determination of As(III) by anodic stripping voltammetry (ASV) using a lateral gold electrode and to study the modifications of the electrode surface during use. Potential waveforms (differential pulse and square wave), potential scan parameters, deposition time, deposition potential and surface cleaning procedure were examined for they effect on arsenic peak intensity and shape. The best responses were obtained with differential pulse potential wave form and diluted 0.25 M HCl as supporting electrolyte. The repeatability, linearity, accuracy and detection limit of the procedure and the interferences of cations and anions in solution were evaluated. The applicability of the procedure for As(III) determination in drinking waters was tested. Cyclic voltammetry (CV) was used to study the electrochemical behaviour of As(III) and for the daily monitoring of electrode surface. Also scanning electron microscopy (SEM) analysis was used to control the electron surface. Finally we evaluated the possibility to apply the equations valid for flow systems also to a stirred system, in order to calculate the number of electrons transferred per molecule during the stripping step.     

Development and optimisation of a novel three‐way extraction technique based on a combination of Soxhlet extraction,membrane assisted solvent extraction and a molecularly imprinted polymer using sludge polycyclic aromatic hydrocarbons as model compounds

A novel technique that integrates extraction and clean‐up into a single step format is reported as part of the search for new sample preparation techniques in the analysis of persistent organic pollutants from complex samples. This was achieved by combining the extraction efficiency of the Soxhlet extractor, the selectivity of a size exclusion membrane and the specificity of a molecularly imprinted polymer for the extraction of polycyclic aromatic hydrocarbons from wastewater sludge followed by quantitation using gas chromatography with time‐of‐flight mass spectrometry. The approach is described as the Soxhlet extraction membrane‐assisted solvent extraction molecularly imprinted polymer technique. This technique was optimised for various parameters such as extraction solvent, reflux time and membrane acceptor phase. The applicability of the developed technique was optimised using a wastewater sludge certified reference material and then tested on real wastewater sludge samples. The method detection limits ranged from 0.14 to 12.86 ng/g with relative standard deviation values for the extraction of the 16 US‐EPA priority polycyclic aromatic hydrocarbons from wastewater sludge samples ranging from 0.78 to 18%. The extraction process was therefore reproducible and showed remarkable selectivity. The developed technique is a promising prospect that can be applied in the analysis of organic pollutants from complex solid samples.     

Design and synthesis of a novel water-soluble Aβ1-42 isopeptide: an efficient strategy for the preparation of Alzheimer's disease-related peptide, Aβ1-42, via O-N intramolecular acyl migration reaction

A novel water-soluble isopeptide of Alzheimer's disease-related peptide Aβ1-42, `26-O-acyl isoAβ1-42', which could efficiently convert to intact Aβ1-42 under physiological conditions via O-N intramolecular acyl migration, was synthesized providing a new system useful for investigation of biological function of Aβ1-42.     

Synthesis,structural characterization,EPR spectroscopy and Hirshfeld surface analysis of a novel Cu2+‐doped 3,14‐diethyl‐2,13‐diaza‐6,17‐diazoniatricyclo[16.4.0.07,12]docosane bis(perchlorate)

Cyclam derivatives and their metal complexes have been found to exhibit an anti‐HIV effect and stimulate the activity of stem cells from bone marrow. The strength of their binding to the CXCR4 receptor correlates with anti‐HIV and stem‐cell activities. Knowledge of the conformation and crystal packing of various macrocyclic metal complexes has become important in developing new effective anti‐HIV drugs. The synthesis and preparation of single crystals of a new Cu²⁺‐doped macrocyclic compound, (3,14‐diethyl‐2,6,13,17‐tetraazatricyclo[16.4.0.0^7,12]docosane)copper(II) bis(perchlorate)–3,14‐diethyl‐2,13‐diaza‐6,17‐diazoniatricyclo[16.4.0.0^7,12]docosane bis(perchlorate) (0.69/0.31), {[Cu(C₂₂H₄₄N₄)](ClO₄)₂}_0.69·(C₂₂H₄₆N₄²⁺·2ClO₄^?)_0.31, is reported. Characterization by X‐ray diffraction analysis shows that the asymmetric unit contains half of a centrosymmetric molecule. The macrocyclic ligand in the compound adopts the most stable trans‐III conformation. The Cu—N distances of 2.015 (3) and 2.047 (3) Å are normal, but the long axial Cu—O bond of 2.795 (3) Å may be due to a combination of the Jahn–Teller effect and the strong in‐plane ligand field. The crystal structure is stabilized by hydrogen bonding between secondary N—H groups, the N atoms of the macrocycle and the O atoms of the perchlorate anions. Hirshfeld surface analysis with 2D (two‐dimensional) fingerprint plots indicates that the main contributions to the crystal packing are from H…H (58.0%) and H…O/O…H (41.9%) interactions. Electron paramagnetic resonance (EPR) properties are also described.