Study of the Function of G‐Rich Aptamers Selected for Lung Adenocarcinoma

Guanine (G)‐rich oligonucleotides have attracted considerable interest as therapeutic agents. Two G‐rich aptamers were selected against epidermal growth factor receptor (EGFR)‐transfected A549 cells, and their G‐rich domains (S13 and S50) were identified to account for the binding of parental aptamers. Circular dichroism (CD) spectra showed that S13 and S50 bound to their targets by forming parallel quadruplexes. Their binding, internalization, and antiproliferation activity in cancer and noncancer cells were investigated by flow cytometry and 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay, and compared with those of nucleolin‐binding AS1411 and thrombin‐binding aptamer. The two truncated aptamers (S13 and S50) have good binding and internalization in cancer cells and noncancer cells; however, only S50, similar to AS1411, shows potent antiproliferation against cancer cells. Our data suggest that tumor‐selective antiproliferation of G‐rich oligonucleotides does not directly depend on the binding of the G‐rich aptamer to cells.     

Comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatography for screening anti‐tumor components from Radix Sophorae flavescentis

Radix Sophorae flavescentis is generally used for the treatment of different stages of prostate cancer in China. It has ideal effects when combined with surgical treatment and chemotherapy. However, its active components are still ambiguous. We devised a comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatography system for screening anti‐prostate cancer components in Radix Sophorae flavescentis . Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validation and optimization the selectivity and suitability of the comprehensive two‐dimensional chromatographic system. Five compounds, sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol were found to have significant retention behaviors on the PC‐3 cell membrane chromatography and were unambiguously identified by time‐of‐flight mass spectrometry. Cell proliferation and apoptosis assays confirmed that all five compounds had anti‐prostate cancer effects. Matrine and xanthohumol had good inhibitory effects, with half maximal inhibitory concentration values of 0.893 and 0.137 mg/mL, respectively. Our comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatographic system promotes the efficient recognition and rapid analysis of drug candidates, and it will be practical for the discovery of prostate cancer drugs from complex traditional Chinese medicines.     

d‐Fructose‐Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting

The high affinity of GLUT5 transporter for d ‐fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d ‐fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four‐step synthesis of a thiol‐group bearing d ‐fructose enables the decoration of a cationic polymer backbone with d ‐fructose via thiol‐ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography. Importantly, a d ‐fructose decoration of 16% renders the polymers water‐soluble and eliminates the cytotoxicity of PEI in noncancer L929 cells, accompanied by a reduced unspecific cellular uptake of the genetic material. In contrast, the cytotoxicity as well as the cell specific uptake is increased for triple negative MDA‐MB‐231 breast cancer cells. Therefore, the introduction of d ‐fructose shows superior potential for cell targeting, which can be assumed to be GLUT5 dependent.

     

Effects of Structural Variations on the Cellular Response and Mechanical Properties of Biocompatible,Biodegradable, and Porous Smectic Liquid Crystal Elastomers

The authors report on series of side‐chain smectic liquid crystal elastomer (LCE) cell scaffolds based on star block‐copolymers featuring 3‐arm, 4‐arm, and 6‐arm central nodes. A particular focus of these studies is placed on the mechanical properties of these LCEs and their impact on cell response. The introduction of diverse central nodes allows to alter and custom‐modify the mechanical properties of LCE scaffolds to values on the same order of magnitude of various tissues of interest. In addition, it is continued to vary the position of the LC pendant group. The central node and the position of cholesterol pendants in the backbone of ε‐CL blocks (alpha and gamma series) affect the mechanical properties as well as cell proliferation and particularly cell alignment. Cell directionality tests are presented demonstrating that several LCE scaffolds show cell attachment, proliferation, narrow orientational dispersion of cells, and highly anisotropic cell growth on the as‐synthesized LCE materials.

     

A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering

In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom‐up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N‐isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm–PDMS substrates optimal for VSMC attachment. To allow long‐term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm–PDMS surfaces were further modified with 3‐aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single‐layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single‐layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue.

     

Thin Poly(Di(Ethylene Glycol)Methyl Ether Methacrylate) Homopolymer Brushes Allow Controlled Adsorption and Desorption of PaTu 8988t Cells

Poly(di(ethylene glycol)methyl ether methacrylate) (PDEGMA) brushes, which are known to suppress protein adsorption and prevent cell attachment, are reported here to possess interesting and tunable thermoresponsive behavior, if the brush thickness is reduced or the grafting density is altered. PDEGMA brushes with a dry ellipsometric thickness of 5 ± 1 nm can be switched from cell adherent behavior at 37 °C to cell nonadherent at 25 °C. This behavior coincides with the temperature‐dependent irreversible adsorption of fibronectin from phosphate saline buffer and proteins present in the cell culture medium, as unveiled by surface plasmon resonance measurements. Unlike for tissue culture polystyrene reference surfaces, swelling of the PDEGMA chains below the lower critical solution temperature results in the absence of paxillin and actin containing cellular filaments responsible for cell attachment. These tunable properties of very thin homopolymer PDEGMA brushes render this system interesting as an alternative thermoresponsive layer for continuous cell culture or enzyme‐free cell culture systems.

     

Aligned Poly(ε‐caprolactone) Nanofibers Guide the Orientation and Migration of Human Pluripotent Stem Cell‐Derived Neurons,Astrocytes, and Oligodendrocyte Precursor Cells In Vitro

Stem cell transplantations for spinal cord injury (SCI) have been studied extensively for the past decade in order to replace the damaged tissue with human pluripotent stem cell (hPSC)‐derived neural cells. Transplanted cells may, however, benefit from supporting and guiding structures or scaffolds in order to remain viable and integrate into the host tissue. Biomaterials can be used as supporting scaffolds, as they mimic the characteristics of the natural cellular environment. In this study, hPSC‐derived neurons, astrocytes, and oligodendrocyte precursor cells (OPCs) are cultured on aligned poly(ε‐caprolactone) nanofiber platforms, which guide cell orientation to resemble that of spinal cord in vivo. All cell types are shown to efficiently spread over the nanofiber platform and orient according to the fiber alignment. Human neurons and astrocytes require extracellular matrix molecule coating for the nanofibers, but OPCs grow on nanofibers without additional treatment. Furthermore, the nanofiber platform is combined with a 3D hydrogel scaffold with controlled thickness, and nanofiber‐mediated orientation of hPSC‐derived neurons is also demonstrated in a 3D environment. In this work, clinically relevant materials and substrates for nanofibers, fiber coatings, and hydrogel scaffolds are used and combined with cells suitable for developing functional cell grafts for SCI repair.

     

Synthesis and characterization of BaGa2O4 and Ba3Co2O6(CO3)0.6 compounds in the search of alternative materials for Proton Ceramic Fuel Cell (PCFC)

BaGa₂O₄ and Ba₃Co₂O₆(CO₃)_0.6 compounds were studied as electrolyte and cathode materials for Proton Ceramic Fuel Cells (PCFC), respectively. Not only BaGa₂O₄ rapidly reacts with atmospheric H₂O and CO₂ and leads to a progressive material decomposition, but it does not present real hydration properties in normal conditions of pressure. On the other hand, the basic cobalt oxocarbonate Ba₃Co₂O₆(CO₃)_0.6 exhibits an interesting tendency for weight uptake and formation of hydrogencarbonate groups in moist heating/cooling conditions. This material was therefore considered for complementary studies in order to confirm its potential use as mixed proton-electron conductor, taking into account the ordered intergrowth of carbonates and face sharing Co-octahedra columns forming a pseudo-one-dimensional structure. Some preliminary results concerning electrochemical properties of the barium cobalt oxocarbonate as a PCFC cathode are also described and show at the moment modest performance, possibly related to a hydrated/carbonated surface layer contribution and/or the lack of electron percolation within the electrode layer.     

Microfibers as Physiologically Relevant Platforms for Creation of 3D Cell Cultures

Microfibers have received much attention due to their promise for creating flexible and highly relevant tissue models for use in biomedical applications such as 3D cell culture, tissue modeling, and clinical treatments. A generated tissue or implanted material should mimic the natural microenvironment in terms of structural and mechanical properties as well as cell adhesion, differentiation, and growth rate. Therefore, the mechanical and biological properties of the fibers are of importance. This paper briefly introduces common fiber fabrication approaches, provides examples of polymers used in biomedical applications, and then reviews the methods applied to modify the mechanical and biological properties of fibers fabricated using different approaches for creating a highly controlled microenvironment for cell culturing. It is shown that microfibers are a highly tunable and versatile tool with great promise for creating 3D cell cultures with specific properties.     

Synthesis and cytotoxicity studies of new 1,2,4-thiadiazole derivatives and their zinc complexes

A new polyfunctional ligand of the thiadiazole family was synthesized. Cytotoxic properties with respect to leukemic cell lines, radiation stability, predicted permeability through the blood–brain barrier and cardiotoxicity of the new ligand and its precursor were determined. New zinc complexes with N-{2-[5-(3-chloro-4-methylphenylamino)-1,2,4-thiadiazol-3-yl]-1-methylethyl}-N-(2,2,6,6-tetramethylpiperidin-4-yl)-amine as the ligand have been obtained.