Размер и форма частиц полипиррола в водных растворах поли-( N-винилпирролидона)

Based on the IR spectroscopy data and on the analysis of rheological characteristics of polypyrrole aqueous suspension stabilized with poly-(N-vinylpyrrolidone) we conjecture that a physical lattice composed with poly-(N-vinylpyrrolidone) is formed, where the lattice points are the polypyrrole chain aggregates interlaced with poly-(N-vinylpyrrolidone) chains. It was shown that there is a hydrogen bond between the constitutional repeating units of poly-(N-vinylpyrrolidone) and polypyrrole. It was determined that the size of the particles of the disperse phase decreases with the increase of poly-(N-vinylpyrrolidone) molecular weight. It was also determined that the size of particles increases with the increase of the mass fraction of polypyrrole aqueous suspension. It was shown that the disperse phase particles are rod-like, and the increase of molecular weight of poly-(N-vinylpyrrolidone) in an aqueous solution results in additional lengthwise stretching of particles. It was also shown that the viscosity of the stabilized poly-(N-vinylpyrrolidone) aqueous suspension follows the Einstein law.На основании данных ИК-спектроскопии и анализа реологических характеристик водной суспензии полипиррола, стабилизированной поли-( N -винилпирролидоном), выдвинуто предположение об образовании физической сетки, формируемой цепями поли-( N -винилпирролидона), узлами которой являются агрегаты цепей полипиррола, переплетенные с цепями поли-( N -винилпирролидона). Установлено уменьшение размера частиц дисперсной фазы при увеличении молекулярной массы поли-( N -винилпирролидона)

Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated Nanoparticles

Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD(2)), providing a target for tumor-specific delivery.Nanoparticles encapsulating miR-34a and conjugated to a GD(2) antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors.These novel findings highlight the potential of anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD(2)-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth

The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Size and shape of polypyrrole particles in aqueous solutions of poly-( <i>N</i>-vinylpyrrolidone)

Based on the IR spectroscopy data and on the analysis of rheological characteristics of polypyrrole aqueous suspension stabilized with poly-(N-vinylpyrrolidone) we conjecture that a physical lattice composed with poly-(N-vinylpyrrolidone) is formed, where the lattice points are the polypyrrole chain aggregates interlaced with poly-(N-vinylpyrrolidone) chains. It was shown that there is a hydrogen bond between the constitutional repeating units of poly-(N-vinylpyrrolidone) and polypyrrole. It was determined that the size of the particles of the disperse phase decreases with the increase of poly-(N-vinylpyrrolidone) molecular weight. It was also determined that the size of particles increases with the increase of the mass fraction of polypyrrole aqueous suspension. It was shown that the disperse phase particles are rod-like, and the increase of molecular weight of poly-(N-vinylpyrrolidone) in an aqueous solution results in additional lengthwise stretching of particles. It was also shown that the viscosity of the stabilized poly-(N-vinylpyrrolidone) aqueous suspension follows the Einstein law