Isatin, 1H-indole-2,3-dione, is a heterocyclic compound of significant importance in medicinal chemistry. It is a synthetically versatile molecule, a precursor for a large number of pharmacologically ...active compounds. Isatin and its derivatives have aroused great attention in recent years due to their wide variety of biological activities, relevant to application as insecticides and fungicides and in a broad range of drug therapies, including anticancer drugs, antibiotics and antidepressants. The purpose of this review is to provide an overview of the pharmacological activities of isatin and its synthetic and natural derivatives. Molecular modifications to tailor the properties of isatin and its derivatives are also discussed.
Vertically aligned silicon nanowire (VA‐SiNW) arrays are emerging as a powerful new tool for gene delivery by means of mechanical transfection. In order to utilize this tool efficiently, ...uncertainties around the required design parameters need to be removed. Here, a combination of nanosphere lithography and templated metal‐assisted wet chemical etching is used to fabricate VA‐SiNW arrays with a range of diameters, heights, and densities. This fabrication strategy allows identification of critical parameters of surface topography and consequently the design of SiNW arrays that deliver plasmid with high transfection efficiency into a diverse range of human cells whilst maintaining high cell viability. These results illuminate the cell‐materials interactions that mediate VA‐SiNW transfection and have the potential to transform gene therapy and underpin future treatment modalities.
An easy‐to‐implement approach to control geometrical parameters in vertically aligned silicon nanowire arrays—which are used in gene delivery by means of mechanical transfection—provided. This is realized by combining nanosphere lithography and templated metal‐assisted wet chemical etching. Optimized nanowire array configurations produce transfection efficiencies approaching 95%.
Insights into cellular uptake of nanoparticles Kafshgari, Morteza Hasanzadeh; Harding, Frances J; Voelcker, Nicolas H
Current drug delivery,
01/2015, Letnik:
12, Številka:
1
Journal Article
Recenzirano
Nanomaterials promise to improve disease diagnosis and treatment by enhancing the delivery of drugs, genes, biomolecules and imaging agents to specific subcellular targets. In order to optimize ...nanomaterial design for this purpose, a comprehensive understanding of how these materials are taken up and transported within the cell is required. In this review, we discuss the endocytic pathways employed by different types of nanoparticles with emphasis on the influence of nanoparticle surface modification. The use of pharmacological inhibition to probe internalization and intracellular trafficking pathways of nanoparticles is critically evaluated. Finally, approaches to target-specific delivery of therapeutics via nanoparticles into the cytoplasm and nucleus are addressed.
Microfluidic 3D cell culture is a promising technology for the screening of drug toxicity profiles. In this study, a bioartificial liver consisting of a surface‐engineered microfluidic silicon chip ...with microtrenches mimicking hepatic sinusoids is shown to extend 3D primary hepatocyte culture and improve in vitro drug screening for hepatotoxicity, with respect to the state‐of‐the‐art literature on this subject. Primary hepatocytes hosted in the 3D heparin‐coated microtrenches (the bioartificial liver) secrete high levels of albumin and urea over 4 weeks. The cytotoxicity of common drugs, namely, acetaminophen, chlorpromazine, and tacrine, was assessed on primary hepatocytes both at day 1 and day 7. The results suggest that mimicking hepatic sinusoids using a microtrench format allows the maintenance of difficult‐to‐culture primary hepatocytes to be extended to 4 weeks and provides an alternative model to animal studies for the screening of the cytotoxicity of new drugs.
The liver is the focal point of numerous studies intended for better understanding the toxicological response of body to novel pharmaceutical entities. A bioartificial liver that supports long‐term primary hepatocyte culture in 3D heparin‐coated microtrenches mimicking the architecture of hepatic sinusoids is developed and tested as predictive in vitro model for hepatotoxicity screening.
A label-free porous silicon (pSi) based, optical biosensor, using both an antibody and aptamer bioreceptor motif has been developed for the detection of insulin. Two parallel biosensors were designed ...and optimised independently, based on each bioreceptor. Both bioreceptors were covalently attached to a thermally hydrosilylated pSi surface though amide coupling, with unreacted surface area rendered stable and low fouling by incorporation of PEG moieties. The insulin detection ability of each biosensor was determined using interferometric reflectance spectroscopy, using a range of different media both with and without serum. Sensing performance was compared in terms of response value, response time and limit of detection (LOD) for each platform. In order to demonstrate the capability of the best performing biosensor to detect insulin from real samples, an in vitro investigation with the aptamer-modified surface was performed. This biosensor was exposed to buffer conditioned by glucose-stimulated human islets, with the result showing a positive response and a high degree of selectivity towards insulin capture. The obtained results correlated well with the ELISA used in the clinic for assaying glucose-stimulated insulin release from donor islets. We anticipate that this type of sensor can be applied as a rapid point-of-use biosensor to assess the quality of donor islets in terms of their insulin production efficiency, prior to transplantation.
•Porous silicon based optical biosensor using interferometric reflectance spectroscopy (IRS) used for insulin detection in islet cell culture.•Surface characterisation using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy performed.•Aptamer and antibody used and compared as bioreceptors.•Application of aptamer modified surface for detection of insulin secreted by human islet on stimulation with glucose.
Ordered arrays of silicon nano- to microscale pillars are used to enable biomolecular trafficking into primary human cells, consistently demonstrating high transfection efficiency can be achieved ...with broader and taller pillars than reported to date. Cell morphology on the pillar arrays is often strikingly elongated. Investigation of the cellular interaction with the pillar reveals that cells are suspended on pillar tips and do not interact with the substrate between the pillars. Although cells remain suspended on pillar tips, acute local deformation of the cell membrane was noted, allowing pillar tips to penetrate the cell interior, while retaining cell viability.
Control over particle self-assembly is a prerequisite for the colloidal templating of lithographical etching masks to define nanostructures. This work integrates and combines for the first time ...bottom-up and top-down approaches, namely, particle self-assembly at liquid–liquid interfaces and metal-assisted chemical etching, to generate vertically aligned silicon nanowire (VA-SiNW) arrays and, alternatively, arrays of nanoscale pores in a silicon wafer. Of particular importance, and in contrast to current techniques, including conventional colloidal lithography, this approach provides excellent control over the nanowire or pore etching site locations and decouples nanowire or pore diameter and spacing. The spacing between pores or nanowires is tuned by adjusting the specific area of the particles at the liquid–liquid interface before deposition. Hence, the process enables fast and low-cost fabrication of ordered nanostructures in silicon and can be easily scaled up. We demonstrate that the fabricated VA-SiNW arrays can be used as in vitro transfection platforms for transfecting human primary cells.
Display omitted
Cell microarrays are a novel platform for the high throughput discovery of new biomaterials. By re-creating a multitude of cell microenvironments on a single slide, this approach can ...identify the optimal surface composition to drive a desired cell response. To systematically study the effects of molecular microenvironments on stem cell fate, we designed a cell microarray based on parallel exposure of mesenchymal stem cells (MSCs) to surface-immobilised collagen I (Coll I) and bone morphogenetic protein 2 (BMP 2). This was achieved by means of a reactive coating on a slide surface, enabling the covalent anchoring of Coll I and BMP 2 as microscale spots printed by a robotic contact printer. The surface between the printed protein spots was passivated using poly (ethylene glycol) bisamine 10,000Da (A-PEG). MSCs were then captured and cultured on array spots composed of binary mixtures of Coll I and BMP 2, followed by automated image acquisition and quantitative, multi-parameter analysis of cellular responses. Surface compositions that gave the highest osteogenic differentiation were determined using Runx2 expression and calcium deposition. Quantitative single cell analysis revealed subtle concentration-dependent effects of surface-immobilised proteins on the extent of osteogenic differentiation obscured using conventional analysis. In particular, the synergistic interaction of Coll I and BMP 2 in supporting osteogenic differentiation was confirmed. Our studies demonstrate the value of cell microarray platforms to decipher the combinatorial interactions at play in stem cell niche microenvironments.
Zero-valent, or elemental, silicon nanostructures exhibit a number of properties that render them attractive for applications in nanomedicine. These materials hold significant promise for improving ...existing diagnostic and therapeutic techniques. This review summarizes some of the essential aspects of the fabrication techniques used to generate these fascinating nanostructures, comparing their material properties and suitability for biomedical applications. We examine the literature in regards to toxicity, biocompatibility and biodistribution of silicon nanoparticles, nanowires and nanotubes, with an emphasis on surface modification and its influence on cell adhesion and endocytosis. In the final part of this review, our attention is focused on current applications of the fabricated silicon nanostructures in nanomedicine, specifically examining drug and gene delivery, bioimaging and biosensing.
Abstract In the field of stem cell technology, future advancements rely on the effective isolation, scale-up and maintenance of specific stem cell populations and robust procedures for their directed ...differentiation. The stem cell microenvironment – or niche – encompasses signal inputs from stem cells, supporting cells and from the extracellular matrix. In this context, the contribution of physicochemical surface variables is being increasingly recognised. This paradigm can be exploited to exert control over cellular behaviour. However, the number of parameters at play, and their complex interactions, presents a formidable challenge in delineating how the decisions of cell fate are orchestrated within the niche. Additionally, in the case of mesenchymal stem cells (MSC), more than one type of stem cell niche has been identified. By employing high throughput screening (HTS) strategies, common and specific attributes of each MSC niche can be probed. Here, we explore biological, chemical and physical parameters that are known to influence MSC self-renewal and differentiation. We then review techniques and strategies that allow the HTS of surface properties for conditions that direct stem cell fate, using MSC as a case study. Finally, challenges in recapturing the niche, particularly its three dimensional nature, in surface-based HTS formats are discussed.
PDF
