Dragos Peptanariu
Romanian Academy
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Featured researches published by Dragos Peptanariu.
Journal of Materials Chemistry B | 2015
Cristina M. Uritu; Cristian Varganici; Laura Ursu; Adina Coroaba; Alina Nicolescu; Andrei Dascalu; Dragos Peptanariu; Daniela Stan; Cristina Ana Constantinescu; Viorel Simion; Manuela Calin; Stelian S. Maier; Mariana Pinteala; Mihail Barboiu
The present study reports fullerene conjugates that act as efficient binders of double stranded DNA (dsDNA) into cytofriendly polyplexes. The conjugates are designed to generate dendrimeric structures, having C60 as the core and bearing linear or branched PEI and polyethyleneglycol (PEG) arms (∼2 kDa). Simple and reproducible synthesis pathways provided C60-PEI and C60-PEG-PEI conjugates. They were able to bind linear and plasmidic dsDNA and they form particulate polyplexes of 50 to 200 nm in diameter. The resulted polyplexes toggle between the anionic and cationic state at nitrogen to phosphorous ratios (N/P) of about 5, as revealed by their zeta potential and became colloidally stable at N/P ratios above 10, as determined by atomic force microscopy (AFM). They are electrophoretically unbreakable starting with N/P ratios of 3 and of 5 when salmon sperm DNA and pEYFP-C1 plasmid, respectively are loaded. Both C60-PEI·pEYFP and C60-PEG-PEI·pEYFP polyplexes are non-cytotoxic against HEK 293T cells in culture and exhibit transfection efficiency better than 25% (N/P ratios above 20) and 6% (N/P ratios above 60) respectively, measured by flow cytometry. For comparison, the commercial SuperFect® from Qiagen (positive control) was able to provide an efficiency of 15-20%, under similar conditions. Moreover, the C60-PEG-PEI conjugate is as performant as the positive control in terms of expression of EYFP reporter gene in cultured cells and exhibited high cytocompatibility, determining cell proliferation up to 200%. Our study proved that C60-PEG-PEI is effective vector for DNA delivery being, in addition, easily synthesizable, practically non-cytotoxic and as efficient the commercially available transfection tools.
Materials Science and Engineering: C | 2016
Gianina Dodi; A. Pala; Eugen Barbu; Dragos Peptanariu; Doina Hritcu; Marcel Popa; Bogdan Tamba
Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV-Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers.
Journal of Materials Chemistry B | 2015
Cristina M. Uritu; Manuela Calin; Stelian S. Maier; Corneliu Cojocaru; Alina Nicolescu; Dragos Peptanariu; Cristina Ana Constantinescu; Daniela Stan; Mihail Barboiu; Mariana Pinteala
Transfection of nucleic acid molecules, large enough to interfere with the genetic mechanisms of active cells, can be performed by means of small carriers, able to collectively collaborate in generating cargocomplexes that could be involved in passive mechanisms of cellular uptake. The present work describes the synthesis, characterization, and evaluation of transfection efficacy of a conjugate molecule, which comprises a cyclic siloxane ring (2,4,6,8-tetramethylcyclotetrasiloxane, cD4 H) as the core, and, on average, 3.76 molecules of 2 kDa polyethyleneimine (PEI) as cationic branches, with an average molecular mass of 7.3 kDa. As demonstrated by in silico molecular modeling and dynamic simulation, the conjugate molecule (cD4 H-AGE-PEI) tends to adopt an asymmetric structure, specific for amphipathic molecules (confirmed by a log P value of -1.902 ± 0.06), that favors a rapid interaction with nucleic acids. The conjugate and the polyplexes with the pEYFP plasmid were proved to be non-cytotoxic, and capable of ensuring transfection yields better than 30%, on HEK 293T cell culture, superior to the value obtained using the SuperFect® reagent. We presume that the increased transfection efficacy originates in the ability of the conjugate to locally tightly encompass pDNA molecules by electrostatic interaction mediated by the short PEI branches, and consequently to expose the siloxane hydrophobic moiety, which decreases the interaction energy with the lipid layers.
International Journal of Biological Macromolecules | 2018
Irina Rosca; Anca Roxana Petrovici; Dragos Peptanariu; Alina Nicolescu; Gianina Dodi; Mihaela Avadanei; Iuliu Cristian Ivanov; Andra Cristina Bostanaru; Mihai Mares; Diana Ciolacu
The aim of this study was to monitor the influence of the fermentation conditions on the exopolysaccharides (EPS) biosynthesis. For this, different culture media compositions were tested on an isolated lactic acid bacteria (LAB) strain, identified by 16S rDNA sequence as being Weissella confusa. It was proved that this bacterial strain culture in MRS medium supplemented with 80g/L sucrose and dissolved in UHT milk produced up to 25.2g/L of freeze-dried EPS, in static conditions, after 48h of fermentative process. Using FTIR and NMR analysis, it was demonstrated that the obtained EPS is a dextran. The thermal analysis revealed a dextran structure with high purity while GPC analysis depicted more fractions, which is normal for a biological obtained polymer. A concentration up to 3mg/mL of dextran proved to have no cytotoxic effect on normal human dermal fibroblasts (NHDF). Moreover, at this concentration, dextran breaks up to 70% of the biofilms formed by the Candida albicans SC5314 strain, and has no antimicrobial activity against standard bacterial strains. Due to their characteristics, these EPS are suitable as hydrophilic matrix for controlled release of drugs in pharmaceutical industry.
Journal of Nanoparticle Research | 2017
Elena-Laura Ursu; Florica Doroftei; Dragos Peptanariu; Mariana Pinteala; Alexandru Rotaru
AbstractSingle-walled carbon nanotubes (SWNTs) are 1D nanostructures with distinct physical and chemical properties that have shown great promise for applications in many fields, including biomedicine. Since for biomedical application the water solubility is crucial and SWNTs have low solubility, various methods (including polymer and biopolymer wrapping, chemical modifications) have been developed to solubilize and disperse them in water. Due to their unique optical properties such as photoluminescence in the NIR and strong resonant Raman signatures, they can be used as nanoprobes in biomedical imaging and phototherapies. Furthermore, decoration of SWNTs with noble metal nanoparticles will induce an excellent surface-enhanced Raman scattering (SERS) effect of the nanoparticles-SWNTs composites, with applications in cell imaging. Herein, we present a new and facile strategy for the DNA-assisted decoration of SWNTs with gold nanoparticles (AuNPs) and their application in SERS imaging. By ultrasonication at room temperature of SWNTs with AuNPs functionalized with synthetic DNA, SWNT-AuNPs nanocomposites with enhanced Raman signal were obtained. Among the important advantages of the proposed method are the presence of the free DNA overhangs around the SWNT-AuNPs suitable for post-synthetic modification of nanocomposite through hybridization of complementary DNA strands containing molecules of interest attached by well-developed bio-conjugation chemistry. Graphical abstractᅟ
Materials Science and Engineering: C | 2019
Daniela Ailincai; Dragos Peptanariu; Mariana Pinteala; Luminita Marin
Dynamic constitutional chemistry has been used to design nonviral vectors for gene transfection. Their design has been thought in order to fulfill ab initio the main requirements for gene therapy. As building blocks were used hyperbranched PEI as hydrophilic part and benzentrialdehyde and a diamine linear siloxane as hydrophobic part, connected through reversible imine linkages. The obtaining of the envisaged structures has been confirmed by NMR and FTIR spectroscopy. The dynamic synthesized amphiphiles proved to be able to self-assemble in nano-sized spherical entities as was demonstrated by TEM and DLS, characterized by a narrow dimensional polydispersity. Agarose gel electrophoresis proved the ability of the synthesized compounds to bind DNA, while TEM revealed the spherical morphology of the formed polyplexes. As a proof of the concept, the nonviral vectors promoted an efficient transfection on HeLa cells, demonstrating that dynamic constitutional chemistry can be an important tool in the development of this domain.
Polymer Chemistry | 2018
Rodinel Ardeleanu; Andrei Dascalu; Andrei Neamtu; Dragos Peptanariu; Cristina M. Uritu; Stelian S. Maier; Alina Nicolescu; Bogdan C. Simionescu; Mihail Barboiu; Mariana Pinteala
This paper describes the philosophy to design, and a procedure to construct polyrotaxane-type gene carriers, together with the proof of their ability to conjunctively cooperate in order to generate cargo-complexes with dsDNA, able to efficiently transfect cultured cells. The main feature of these entities is their functionality as a cargo-complex that chemomimic the histones, and morphomimic the nucleosome. The polyrotaxane contains a PEG axle end-capped with silatrane cages, allowing the threading of nine cyclodextrin units, functionalized with polyethylenimines (PEI, 2 kDa). The obtained ROT-PEI multivalent architecture is similar to a giant PEI polycation, but devoid of the toxicity of large PEIs. To increase the cargo-complexes’ versatility and to reduce their cytotoxicity, the study has been complemented with two other types of carriers: (i) including a mixture of PEI and short PEG molecules (ROT-PEI-PEG750), and (ii) with PEI branches post-decorated with guanidine or arginine (ROT-PEI-G; ROT-PEI-Arg). The molecular geometry and the overall interactions of the synthesized carriers were investigated in silico. The experimental DNA binding capacity of these carriers in relationship with size, morphology and electrical charge was evaluated. The in vitro tests, showing the cytotoxicity and transfection efficiency of the investigated carriers, provided new information on gene vector design.
Journal of Materials Chemistry B | 2017
Andrei Dascalu; R. Ardeleanu; A. Neamtu; Stelian S. Maier; Cristina M. Uritu; Alina Nicolescu; M. Silion; Dragos Peptanariu; Manuela Calin; Mariana Pinteala
Efficient tools are still being searched for to substitute the viral vectors in nucleic acid delivery applications. One of the most severe constraints in producing them is related to the strict reproducibility of their molecular characteristics, which is ensured through the synthesis. In this work, we report an original route to obtain polycationic nanoentities with low variability, which are able to act as cooperating carriers for dsDNA complexation and transport. The carriers are synthesized by rigorous conjugation of β-cyclodextrin (β-CD) with precise ratios of 2 kDa branched poly(ethyleneimine) (b-PEI) and 0.75 kDa poly(ethylene glycol) (PEG). Low cytotoxicity was the key parameter of the carrier design, besides the highest possible transfection ability, and both of these features were proven by HeLa cell culture assays. A reporter gene which induces the expression of green fluorescent protein (GFP), inserted in a plasmid, was used to perform the necessary quantitative measurements. In silico molecular modelling guided the carrier design and confirmed the functional mimicry of histones in the tight and compact nucleosome-like spiral packaging of dsDNA. The carrier molecules, synthesized with high reproducibility, are expected to be feasible for application in gene transfection.
Chemical Communications | 2015
Lilia Clima; Dragos Peptanariu; Mariana Pinteala; Adrian Salic; Mihail Barboiu
Organic and Biomolecular Chemistry | 2015
Ioana-Andreea Turin-Moleavin; Florica Doroftei; Adina Coroaba; Dragos Peptanariu; Mariana Pinteala; Adrian Salic; Mihail Barboiu