Enzyme-activated intracellular drug delivery with tubule clay nanoformulation

Fabrication of stimuli-triggered drug delivery vehicle s is an important milestone in treating cancer. Here we demonstrate the selective anticancer drug delivery into human cells with biocompatible 50-nm diameter halloysite nanotube carriers. Physically-adsorbed dextrin end stoppers secure the intercellular release of brilliant green. Drug-loaded nanotubes penetrate through the cellular membranes and their uptake efficiency depends on the cells growth rate. Intercellular glycosyl hydrolases-mediated decomposition of the dextrin tube-end stoppers triggers the release of the lumen-loaded brilliant green, which allowed for preferable elimination of human lung carcinoma cells (Crossed D sign 549) as compared with hepatoma cells (Hep3b). The enzyme-activated intracellular delivery of brilliant green using dextrin-coated halloysite nanotubes is a promising platform for anticancer treatment

Surface-modified magnetic human cells for scaffold-free tissue engineering

We report the magnetically-facilitated scaffold-free assembly of lung tissue mimicking two-layered multicellular clusters. Polymer-stabilized magnetic nanoparticles were deposited on surfaces of viable human cells (A549 and skin fibroblasts), allowing the formation of two-layered porous tissue prototypes. © 2013 The Royal Society of Chemistry

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

© 2015, Tsinghua University Press and Springer-Verlag Berlin Heidelberg. Regenerative medicine requires new ways to assemble and manipulate cells for fabrication of tissue-like constructs. Here we report a novel approach for cell surface engineering of human cells using polymer-stabilized magnetic nanoparticles (MNPs). Cationic polyelectrolyte-coated MNPs are directly deposited onto cellular membranes, producing a mesoporous semi-permeable layer and rendering cells magnetically responsive. Deposition of MNPs can be completed within minutes, under cell-friendly conditions (room temperature and physiologic media). Microscopy (TEM, SEM, AFM, and enhanced dark-field imaging) revealed the intercalation of nanoparticles into the cellular microvilli network. A detailed viability investigation was performed and suggested that MNPs do not inhibit membrane integrity, enzymatic activity, adhesion, proliferation, or cytoskeleton formation, and do not induce apoptosis in either cancer or primary cells. Finally, magnetically functionalized cells were employed to fabricate viable layered planar (two-cell layers) cell sheets and 3D multicellular spheroids. [Figure not available: see fulltext.

Nano-labelled cells - A functional tool in biomedical applications

© 2014 Elsevier Ltd. All right reserved. Nanotechnology offers an unprecedented number of opportunities for biomedical research, utilizing the unusual functionalities of nanosized materials. Here we describe the recent advances in fabrication and utilization of nanoparticle-labelled cells. We present a brief overview of the most promising techniques, namely layer-by-layer polyelectrolyte assembly on cells and intracellular and extracellular labelling with magnetic nanoparticles. Several important practical application of nanofucntionalized cells, including tissue engineering and tumour therapy, are reviewed

A direct technique for magnetic functionalization of living human cells

Functionalized living cells are regarded as effective tools in directed cell delivery and tissue engineering. Here we report the facile functionalization of viable isolated HeLa cells with superparamagnetic cationic nanoparticles via a single-step biocompatible process. Nanoparticles are localized on the cellular membranes and do not penetrate into the cytoplasm. The magnetically responsive cells are viable and able to colonize and grow on substrates. Magnetically facilitated microorganization of functionalized cells into viable living clusters is demonstrated. We believe that the technique described here may find a number of potential applications in cell-based therapies and in development of whole-cell biosensors. © 2011 American Chemical Society

Stabilized dye-pigment formulations with platy and tubule nanoclays

[EN] Alumosilicate materials of different morphologies, such as platy and tubule nanoclays, may serve as an efficient, protective encasing for colored organic substances and nanoparticles. The adsorption of dyes onto the nanoclays increases their stability against thermal, oxidative, and acid¿base-induced decomposition. Natural organic dyes form stable composites with clays, thus allowing for ¿green¿ technology in production of industrial nanopigments. In the presence of high-surface-area alumosilicate materials, semiconductor nanoparticles known as quantum dots are stabilized against agglomeration during their colloid synthesis, resulting in safe colors. The highly dispersed nanoclays such as tubule halloysite can be employed as biocompatible carriers of quantum dots for the dual labeling of living human cells¿both for dark-field and fluorescence imaging. Therefore, complexation of dyes with nanoclays allows for new, stable, and inexpensive color formulations.Y.L., V.V., A.S., and A.N. thank the Ministry of Education and Science of the Russian Federation (grant 14.Z50.31.0035) for funding this work. Authors are grateful to Mikhail S. Kotelev (Gubkin University) for the TEM micrographs. The human cell labeling work was performed by RF and ER according to the Russian Government Program of Competitive Growth of Kazan Federal University. The authors also thank the Spanish Ministry of Economy and Competitiveness for funding Projects DPI2011-30090-C02-02 and DPI2015-68514-RMicó-Vicent, B.; Martínez-Verdú, FM.; Novikov, A.; Stavitskaya, A.; Vinokurov, V.; Rozhina, E.; Fakhrullin, R.... (2017). Stabilized dye-pigment formulations with platy and tubule nanoclays. Advanced Functional Materials. 28(27):1-9. https://doi.org/10.1002/adfm.201703553S192827Massos, A., & Turner, A. (2017). Cadmium, lead and bromine in beached microplastics. 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Properties and applications of halloysite nanotubes: recent research advances and future prospects. Applied Clay Science, 112-113, 75-93. doi:10.1016/j.clay.2015.05.001Cavallaro, G., Lazzara, G., & Milioto, S. (2012). Exploiting the Colloidal Stability and Solubilization Ability of Clay Nanotubes/Ionic Surfactant Hybrid Nanomaterials. The Journal of Physical Chemistry C, 116(41), 21932-21938. doi:10.1021/jp307961qMicó-Vicent, B., Jordán, J., Martínez-Verdú, F., & Balart, R. (2016). A combination of three surface modifiers for the optimal generation and application of natural hybrid nanopigments in a biodegradable resin. Journal of Materials Science, 52(2), 889-898. doi:10.1007/s10853-016-0384-8R. Price, B. P. Gaber, Y. Lvov, R. (2001). In-vitro release characteristics of tetracycline HCl, khellin and nicotinamide adenine dineculeotide from halloysite; a cylindrical mineral. 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Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth

Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined. Here we show that mechanical forces, associated with increased body weight at the end of adolescence, trigger the mechanoreceptor PIEZO1 and thereby mediate enhanced production of the kinase FAM20C in osteoblasts. FAM20C, the major kinase of the secreted phosphoproteome, phosphorylates dentin matrix protein 1, previously identified as a key factor in bone mineralization. Thereupon, dentin matrix protein 1 is secreted from osteoblasts in a burst-like manner. Extracellular dentin matrix protein 1 inhibits vascular endothelial growth factor signalling by preventing phosphorylation of vascular endothelial growth factor receptor 2. Hence, secreted dentin matrix protein 1 transforms type H vessels into type L to limit bone growth activity and enhance bone mineralization. The discovered mechanism may suggest new options for the treatment of diseases characterised by aberrant activity of bone and vessels such as osteoarthritis, osteoporosis and osteosarcoma