Institute of Biophysics and Cell Engineering of NASB

Minsk, Belarus

Institute of Biophysics and Cell Engineering of NASB

Minsk, Belarus
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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.


PubMed | CIBER ISCIII, University of Lodz, Russian Academy of Sciences, University of Paris Descartes and 3 more.
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2015

This paper examines a perspective to use newly engineered nanomaterials as effective and safe carriers for gene therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus, and carbosilane) were complexed with anticancer siRNA and the biophysical properties of the dendriplexes created were analyzed. The potential of the dendrimers as nanocarriers for anticancer Bcl-xl, Bcl-2, Mcl-1 siRNAs and additionally a scrambled sequence siRNA has been explored. Dendrimer/siRNA complexes were characterised by various methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. In this part of study, the transfection of complexes in HeLa and HL-60 cells was analyzed using both single apoptotic siRNAs and a mixture (cocktail) of them. Cocktails were more effective than single siRNAs, allowing one to decrease siRNAs concentration in treating cells. The dendrimers were compared as siRNA carriers, the most effective being the phosphorus-based ones. However, they were also the most cytotoxic on their own, so that in this regard the application of all dendrimers in anticancer therapy will be discussed.


PubMed | Institute of Biophysics and Cell Engineering of NASB, Technical University of Lodz and University of Lodz
Type: | Journal: Colloids and surfaces. B, Biointerfaces | Year: 2015

Protein absorption at the surface of big nanoparticles and formation of protein corona can completely change their biological properties. In contrast, we have studied the binding of small nanoparticles - dendrimers - to proteins and the formation of their nanoparticle corona. Three different types of interactions were observed. (1) If proteins have rigid structure and active site buried deeply inside, the nanoparticle corona is unaffected. (2) If proteins have a flexible structure and their active site is also buried deeply inside, the nanoparticle corona affects protein structure, but not enzymatic activity. (3) The nanoparticle corona changes both the structure and enzymatic activity of flexible proteins that have surface-based active centers. These differences are important in understanding interactions taking place at a bio-nanointerface.


PubMed | Institute of Biophysics and Cell Engineering of NASB, French National Center for Scientific Research and University of Lodz
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2016

In the field of nanotechnology, dendrimers represent a new class of highly branched macromolecules that is receiving a stimulating and rising interest. The structural organization of these synthetic macromolecules provides promising opportunities for using them as nano-carriers of drugs or gene material to be delivered to the target cells. For applications of dendrimers as drug carriers, analysis of their specific interactions with biological structures at molecular level is very important. This paper describes the molecular interactions between cationic phosphorus dendrimers of third and fourth generation (CPD G3 and CPD G4) and 3 plasma regulatory proteins, namely aspartate transaminase, alkaline phosphatase and l-lactic dehydrogenase. Dendrimer-protein interactions were studied using spectrofluorimetric, circular dichroism and dynamic light scattering techniques. Their morphology in the presence or absence of dendrimers was examined by transmission electron microscopy. The results suggest that both dendrimers form positively charged complexes with HIV-derived peptides. The circular dichroism spectra show that these dendrimers can significantly change the secondary structure of proteins, indicating formation of protein/dendrimer complexes.


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 Ústí 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.


PubMed | Institute of Biophysics and Cell Engineering of NASB, French National Center for Scientific Research, Russian Academy of Sciences, University of Lodz and University of Alcalá
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2015

This paper examines a perspective on the use of newly engineered nanomaterials as effective and safe carriers of genes for the therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus and carbosilane) were complexed with anticancer siRNA and their biophysical properties of the dendriplexes analyzed. The potential of the dendrimers as nanocarriers for anticancer siBcl-xl, siBcl-2, siMcl-1 siRNAs and a siScrambled sequence was explored. Dendrimer/siRNA complexes were characterized by methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. Some of the experiments were done with heparin to check if siRNA can be easily disassociated from the complexes, and whether released siRNA maintains its structure after interaction with the dendrimer. The results indicate that siRNAs form complexes with all the dendrimers tested. Oligoribonucleotide duplexes can be released from dendriplexes after heparin treatment and the structure of siRNA is maintained in the case of PAMAM or carbosilane dendrimers. The dendrimers were also effective in protecting siRNA from RNase A activity. The selection of the best siRNA carrier will be made based on cell culture studies (Part B).


Szewczyk M.,University of Lodz | Drzewinska J.,University of Lodz | Dzmitruk V.,Institute of Biophysics and Cell Engineering of NASB | Shcharbin D.,Institute of Biophysics and Cell Engineering of NASB | And 3 more authors.
Journal of Physical Chemistry B | Year: 2012

There are several barriers to the application of dendriplexes formed by poly(propylene imine) dendrimers and genetic material for gene therapy. One limitation is their interaction with extracellular matrix components such as glucosaminoglycans. These can displace the genetic material from the dendriplexes, affecting their transfection activity. In this study, we analyzed the interaction between dendriplexes and the four main glucosaminoglycans (heparin, heparan sulfate, chondroitin sulfate, and hyaluronic acid) by fluorescence polarization and gel electrophoresis. Dendriplexes were formed by combining three anti-HIV antisense oligodeoxynucleotides with three poly(propylene imine) dendrimers of the fourth generation: unmodified and partially modified with maltose and maltotriose (open shell glycodendrimers). The data showed that the effect of glucosaminoglycans on dendriplexes depends on the glucosaminoglycan type and the oligosaccharide serving as the surface group of the dendrimer. Heparin at physiological concentrations destroys dendriplexes formed by open shell glycodendrimers, but dendriplexes based on unmodified poly(propylene imine) dendrimers are stable in its presence. The other glucosaminoglycans at physiological concentrations cannot destroy dendriplexes formed by any of the dendrimers studied. © 2012 American Chemical Society.


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.


Nowacka O.,University of Lodz | Shcharbin D.,Institute of Biophysics and Cell Engineering of NASB | Klajnert-Maculewicz B.,University of Lodz | Bryszewska M.,University of Lodz
Colloids and Surfaces B: Biointerfaces | Year: 2014

Dendrimers' action on proteins and peptides has a dual and controversial character. On one hand, they dissolve prion protein and amyloid fibrils aggregates, which are otherwise only soluble in solvents containing both detergents and high denaturant concentrations. On the other hand they are able to destabilize proteins in generation dependent manner. In present work we estimated the influence of small concentrations (up to 1.4. μg/ml) of cationic, neutral and anionic poly(amidoamine) dendrimers of 3rd and 4th generations on dithiotreitol induced aggregation of insulin. It was found that cationic dendrimers decreased the insulin aggregation, while anionic and neutral ones did not. At the same time, destabilizing effect of dendrimers on insulin structure was not observed. The conclusion was made that small concentrations of dendrimers can be applied to prevent or decrease the formation of misfolded structures of protein. © 2014 Elsevier B.V.


PubMed | Institute of Biophysics and Cell Engineering of NASB
Type: Journal Article | Journal: Expert opinion on therapeutic patents | Year: 2015

The beginning of the nano-era started with the appearance of artificial nanosized supramolecular systems called nanomaterials and nanoparticles (NPs).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.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.

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