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Shcharbin D.,Institute of Biophysics and Cell Engineering of NASB | Shakhbazau A.,University of Calgary | Bryszewska M.,University of Lodz
Expert Opinion on Drug Delivery | Year: 2013

Introduction: Gene therapy is one of the most effective ways to treat major infectious diseases, cancer and genetic disorders. It is based on several viral and non-viral systems for nucleic acid delivery. The number of clinical trials based on application of non-viral drug and gene delivery systems is rapidly increasing. Areas covered: This review discusses and summarizes recent advances in poly(amidoamine) dendrimers as effective gene carriers in vitro and in vivo, and their advantages and disadvantages relative to viral vectors and other non-viral systems (liposomes, linear polymers) are considered. Expert opinion: In this regard, dendrimers are non-immunogenic and have the highest efficiency of transfection among other non-viral systems, and none of the drawbacks characteristic for viral systems. The toxicity of dendrimers both in vitro and in vivo is an important question that has been addressed on many occasions. Several non-toxic and efficient multifunctional dendrimer-based conjugates for gene delivery, along with modifications to improve transfection efficiency while decreasing cytotoxicity, are discussed. Twelve paradigms that affected the development of dendrimer-based gene delivery are described. The conclusion is that dendrimers are promising candidates for gene delivery, but this is just the beginning and further studies are required before using them in human gene therapy. © Informa UK, Ltd. Source

Borisevich N.,B. I. Stepanov Institute of Physics | Loznikova S.,Institute of Biophysics and Cell Engineering of NASB | Sukhodola A.,B. I. Stepanov Institute of Physics | Halets I.,Institute of Biophysics and Cell Engineering of NASB | And 2 more authors.
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2013

Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO4 in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO4 decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate. © 2012 Elsevier B.V. All rights reserved. Source

Shakhbazau A.,University of Calgary | Mishra M.,University of Calgary | Chu T.-H.,University of Calgary | Brideau C.,University of Calgary | And 10 more authors.
Macromolecular Bioscience | Year: 2015

Dendrimers and dendriplexes, highly branched synthetic macromolecules, have gained popularity as new tools for a variety of nanomedicine strategies due to their unique structure and properties. We show that fluorescent phosphorus dendrimers are well retained by bone marrow-derived macrophages and exhibit robust spectral shift in its emission in response to polarization conditions. Fluorescence properties of this marker can also assist in identifying macrophage presence and phenotype status at different time points after spinal cord injury. Potential use of a single dendrimer compound as a drug/siRNA carrier and phenotype-specific cell tracer offers new avenues for enhanced cell therapies combined with monitoring of cell fate and function in spinal cord injury. Fluorescent phosphorus dendrimer is readily internalized and maintained by bone marrow-derived macrophages, making it a useful cytoplasmic tracer. Sensitivity of dendrimer emission profile to the macrophage physiological status generates distinct spectral phenotypes, a feature which may offer new strategies for targeted release of therapeutic cargos, and assist in tracing macrophage plasticity in longitudinal studies in vitro and in vivo. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Pedziwiatr-Werbicka E.,University of Lodz | Shcharbin D.,University of Lodz | Shcharbin D.,Institute of Biophysics and Cell Engineering of NASB | Maly J.,J.E. Purkyne University in Usti nad Labem | And 10 more authors.
Journal of Biomedical Nanotechnology | Year: 2012

The success of gene therapy depends on the development of suitable carriers, and because of their architecture dendrimers are promising tools for gene delivery. This research concerns the use of second generation carbosilane dendrimers as carriers for anti-HIV oligodeoxynucleotides (ODNs). The aim was to characterize complexes formed by positively charged dendrimers and negatively charged oligonucleotides using a fluorescence method, laser Doppler electrophoresis, dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM) and molecular modeling. The zeta-potential of ODNs increased from -25 mV to positive values after the addition of dendrimers. DLS and TEM revealed that the diameters of dendriplexes ranged from 75 to 240 nm and from 50 to 260 nm, respectively, and this was dependent on the type of dendrimer and the molar ratios of the complexes formed; complexes were stable for between 100 and 300 minutes. AFM measurements and molecular modeling studies were carried out to determine the structure and size of dendriplexes. The physicochemical properties of the dendriplexes studied and data from previous research suggest that carbosilane dendrimers are good candidates for nucleic acid delivery. Copyright © 2012 American Scientific Publishers All rights reserved. Source

Shcharbin D.,Institute of Biophysics and Cell Engineering of NASB | Shakhbazau A.,University of Calgary | Mignani S.,University of Paris Descartes | Majoral J.-P.,French National Center for Scientific Research | Bryszewska M.,University of Lodz
Expert Opinion on Therapeutic Patents | Year: 2015

Introduction: The beginning of the nano-era started with the appearance of artificial nanosized supramolecular systems called nanomaterials and nanoparticles (NPs).Areas covered: In the present review, we have analyzed the patents on phosphorus-based nanomaterials (fullerenes, quantum dots [QDs], graphene, liposomes, dendrimers, gold and silver NPs) in biology and medicine. Their impact in treatment of cancer, viral infections and cardiovascular diseases is discussed.Expert opinion: Liposomes and dendrimers had the highest number of biomedical patents. The third candidates were QDs and the fourth and fifth were gold and silver NPs. Fullerenes and carbon nanotubes have the fewest applications in biology and medicine. Thus, our first conclusion was about the 'unifying nanotoxicology paradigm', that 'soft' NPs are significantly more biocompatible than 'hard' NPs. There has been a trend of these nanomaterials being applied in medicine drug and gene delivery, visualization of cells and pathologic processes, using them as antivirals and antimicrobials, contrast agents, antioxidants and photosensitizers. It was unexpected that no patents were found in which phosphorus NPs were used in 3D printing of bones and other biological tissues. The conclusion reached is that nanomaterials are promising tools in future medical applications. © 2015 Informa UK, Ltd. Source

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