Identification of extracellular nanoparticle subsets by nuclear magnetic resonance

Exosomes are a subset of secreted lipid envelope-encapsulated extracellular vesicles (EVs) of 50–150 nm diameter that can transfer cargo from donor to acceptor cells. In the current purification protocols of exosomes, many smaller and larger nanoparticles such as lipoproteins, exomers and microvesicles are typically co-isolated as well. Particle size distribution is one important characteristics of EV samples, as it reflects the cellular origin of EVs and the purity of the isolation. However, most of the physicochemical analytical methods today cannot illustrate the smallest exosomes and other small particles like the exomers. Here, we demonstrate that diffusion ordered spectroscopy (DOSY) nuclear magnetic resonance (NMR) method enables the determination of a very broad distribution of extracellular nanoparticles, ranging from 1 to 500 nm. The range covers sizes of all particles included in EV samples after isolation. The method is non-invasive, as it does not require any labelling or other chemical modification. We investigated EVs secreted from milk as well as embryonic kidney and renal carcinoma cells. Western blot analysis and immuno-electron microscopy confirmed expression of exosomal markers such as ALIX, TSG101, CD81, CD9, and CD63 in the EV samples. In addition to the larger particles observed by nanoparticle tracking analysis (NTA) in the range of 70–500 nm, the DOSY distributions include a significant number of smaller particles in the range of 10–70 nm, which are visible also in transmission electron microscopy images but invisible in NTA. Furthermore, we demonstrate that hyperpolarized chemical exchange saturation transfer (Hyper-CEST) with ¹²⁹Xe NMR indicates also the existence of smaller and larger nanoparticles in the EV samples, providing also additional support for DOSY results. The method implies also that the Xe exchange is significantly faster in the EV pool than in the lipoprotein/exomer pool.

Diffusion and xenon NMR based methods to determine a very broad range of sizes and sub-sets of extracellular vesicles.     

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)–cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.     

The Compressibility of pH‐Sensitive Microgels at the Oil–Water Interface: Higher Charge Leads to Less Repulsion

pH‐responsive microgels are unique stabilizers for stimuli‐sensitive emulsions that can be broken on demand by changing the pH value. However, recent experiments have indicated that electrostatic interactions play a different role to that in conventional Pickering emulsions. The influence of charges on the interactions between microgels at the oil–water interface is now described. Compression isotherms of microgels with different charge density and architecture were determined in a Langmuir trough, and counter‐intuitive results were obtained: Charged microgels can be compressed more easily than uncharged microgels. The compressibility of microgels is thus not determined by direct Coulomb repulsion. Instead, the different swelling of the microgels in the charged and the uncharged states is proposed to be the key parameter.     

Synthesis of tapioca cellulose-based poly(hydroxamic acid) ligand for heavy metals removal from water

A graft copolymerization was performed using free radical initiating process to prepare the poly(methyl acrylate) grafted copolymer from the tapioca cellulose. The desired material is poly(hydroxamic acid) ligand, which is synthesized from poly(methyl acrylate) grafted cellulose using hydroximation reaction. The tapioca cellulose, grafted cellulose and poly(hydroxamic acid) ligand were characterized by Infrared Spectroscopy and Field Emission Scanning Electron Microscope. The adsorption capacity with copper was found to be good, 210 mg g^?1 with a faster adsorption rate (t_1/2 = 10.5 min). The adsorption capacities for other heavy metal ions were also found to be strong such as Fe³⁺, Cr³⁺, Co³⁺ and Ni²⁺ were 191, 182, 202 and 173 mg g^?1, respectively at pH 6. To predict the adsorption behavior, the heavy metal ions sorption onto ligand were well-fitted with the Langmuir isotherm model (R² > 0.99), which suggest that the cellulose-based adsorbent i.e., poly(hydroxamic acid) ligand surface is homogenous and monolayer. The reusability was checked by the sorption/desorption process for six cycles and the sorption and extraction efficiency in each cycle was determined. This new adsorbent can be reused in many cycles without any significant loss in its original removal performances.     

Cationic polymerization of vinyl ether with a benzoate pendant: The formation of long‐lived polymers and the identification of side reactions

The cationic polymerization of 2‐[4‐(methoxycarbonyl)phenoxy] ethyl vinyl ether, a vinyl ether with a benzoate pendant, was carried out with an HCl/ZnCl₂ initiating system in methylene chloride at −15 °C. The polymerization proceeded with living/long‐lived propagating species to produce polymers with controlled molecular weights and relatively narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight ≤ ∼1.4), despite the formation of a small amount of oligomeric products during the polymerization. The structural analysis showed that the lowest molecular weight oligomer had the structure CH₃CH(OCH₂CH₂OC₆H₄COOCH₃)OCH₂CH₂OC₆H₄COOCH₃. The oligomer was formed by the reaction of the monomeric propagating species with the alcohol produced by the side reaction of the active species with water as an impurity during the early stage of polymerization. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4362–4372, 2000     

Remarkable effect of pre‐organization on the self assembly in chiral liquid crystals

In this article, liquid crystal phases possessing a helical molecular assembly, including frustrated three dimensional (3D) structures, are overviewed. Then, the chirality‐originated superstructures in liquid crystals studied by the author are reviewed. The importance of the concept of “pre‐organization” is highlighted, thus, molecular design producing a strong chiral effect has been proposed. Dichiral twin materials have been prepared systematically based on this concept, and correlation between molecular architectures and resulting frustrated liquid crustal phases, such as smectic blue, cubic, tetragonal smectic Q, and sponge phases, has been investigated. An electrically induced anisotropic birefringent structure in the chiral isotropic phase and a photoinduced 3D‐3D phase transition in the smectic Q phase are introduced as possible application on the basis of the frustrated chiral 3D structured liquid crystal phases. A new type of chiral effect inducing the structural anisotropy in the 3D cubic structure of soft material is also described. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 340–355; 2009: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.200900029     

Platform for Highly Sensitive Alkaline Phosphatase‐Based Immunosensors Using 1‐Naphthyl Phosphate and an Avidin‐Modified Indium Tin Oxide Electrode

We report a versatile platform for highly sensitive alkaline phosphatase (ALP)‐based electrochemical biosensors that uses an avidin‐modified indium tin oxide (ITO) electrode as a sensing electrode and 1‐naphthyl phosphate (NPP) as an ALP substrate. Almost no electrocatalytic activity of NPP and good electrocatalytic activity of 1‐naphthol (ALP product) on the ITO electrodes allow a high signal‐to‐background ratio. The effective surface covering of avidin on the ITO electrodes allows very low levels of nonspecific binding of proteins to the sensing electrodes. The platform technology is used to detect mouse IgG with a detection limit of 1.0 pg/mL.     

Two-Dimensional Supramolecular Polymerization of a Bis-Urea Macrocycle into a Brick-Like Hydrogen-Bonded Network

We report on a dendronized bis-urea macrocycle 1 self-assembling via a cooperative mechanism into two-dimensional (2D) nanosheets formed solely by alternated urea-urea hydrogen bonding interactions. The pure macrocycle self-assembles in bulk into one-dimensional liquid-crystalline columnar phases. In contrast, its self-assembly mode drastically changes in CHCl₃ or tetrachloroethane, leading to 2D hydrogen-bonded networks. Theoretical calculations, complemented by previously reported crystalline structures, indicate that the 2D assembly is formed by a brick-like hydrogen bonding pattern between bis-urea macrocycles. This assembly is promoted by the swelling of the trisdodecyloxyphenyl groups upon solvation, which frustrates, due to steric effects, the formation of the thermodynamically more stable columnar macrocycle stacks. This work proposes a new design strategy to access 2D supramolecular polymers by means of a single non-covalent interaction motif, which is of great interest for materials development.     

电解质对两性药物分子盐酸氯丙嗪的胶团生长的影响

The effect of electrolytes on the micellar behavior of an amphiphilic drug,chlorpromazine(CPZ)hydroehloride,was studied using cloud point(CP)and dye solubilization techniques.In the presence of KBr,increase because of deprotonation of drug molecules at high pH. The visible absorbance increased(due to dye solubilization)with the increase in pH from 6.5 to 6.9,which indicated micellar growth.At fixed pH(6.7),addition of inorganic salts(KF,KC1,effecfiveness being in the order:F-Na >K ,which Was explained by considering cognizance of their hydrated radii.Compared with anions,their effect was small.Increase in[CPZ]caused micellar growth and hence the CP as well as the visible absorbance increased.The overall behavior Was discussed in terms of electrostatic interactions and micellar growth.     

Linear hydrogen‐bonded molecular tapes in the cocrystals of squaric acid with 4,4′‐dipyridylacetylene and 1,2‐bis(4‐pyridyl)ethylene

The title compounds, 4,4′‐(ethyne‐1,2‐diyl)­dipyridinium bis(squarate), C₁₂H₁₀N₂²⁺·2C₄HO₄^?, and 4,4′‐(ethene‐1,2‐diyl)­dipyridinium bis­(squarate), C₁₂H₁₂N₂²⁺·2C₄HO₄^?, are isomorphous and crystallize in space group P. The cocrystals contain linear hydrogen‐bonded molecular tape structures along the [120] direction. The squarate monoanions form a ten‐membered dimer linked by two intermolecular O—H?O hydrogen bonds. Each component mol­ecule forms a segregated stack along the c axis. The bond lengths of the squarate monoanion indicate delocalization of the enolate anion.