Alexandru Rotaru
@icmpp.ro
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Insa Klemt, Oleg Varzatskii, Roman Selin, Serhii Vakarov, Vladyslava Kovalska, Galyna Bila, Rostyslav Bilyy, Yan Voloshin, Itziar Cossío Cuartero, Andrés Hidalgo,et al.
American Chemical Society (ACS)
The amount of unfolded proteins is increased in cancer cells, leading to endoplasmic reticulum (ER) stress. Therefore, cancer cells are sensitive to drugs capable of further enhancing ER stress. Examples of such drugs include the clinically approved proteosome inhibitors bortezomib and carfilzomib. Unfortunately, the known ER stress inducers exhibit dose-limiting side effects that justify the search for better, more cancer-specific drugs of this type. Herein, we report on FeC 2, which binds to unfolded proteins prevents their further processing, thereby leading to ER stress and ROS increase in cancer cells, but not in normal cells. FeC 2 exhibits low micromolar toxicity toward human acute promyelocytic leukemia HL-60, Burkitt's lymphoma BL-2, T-cell leukemia Jurkat, ovarian carcinoma A2780, lung cancer SK-MES-1, and murine lung cancer LLC1 cells. Due to the cancer-specific mode of action, 2 is not toxic in vivo up to the dose of 147 mg/kg, does not affect normal blood and bone marrow cells at the therapeutically active dose, but strongly suppresses both primary tumor growth (confirmed in Nemeth-Kellner lymphoma and LLC1 lung cancer models of murine tumor) and spreading of metastases (LLC1).
Monica-Cornelia Sardaru, Narcisa-Laura Marangoci, Rosanna Palumbo, Giovanni N. Roviello, and Alexandru Rotaru
MDPI AG
Raman nanoparticle probes are a potent class of optical labels for the interrogation of pathological and physiological processes in cells, bioassays, and tissues. Herein, we review the recent advancements in fluorescent and Raman imaging using oligodeoxyribonucleotide (ODN)-based nanoparticles and nanostructures, which show promise as effective tools for live-cell analysis. These nanodevices can be used to investigate a vast number of biological processes occurring at various levels, starting from those involving organelles, cells, tissues, and whole living organisms. ODN-based fluorescent and Raman probes have contributed to the achievement of significant advancements in the comprehension of the role played by specific analytes in pathological processes and have inaugurated new possibilities for diagnosing health conditions. The technological implications that have emerged from the studies herein described could open new avenues for innovative diagnostics aimed at identifying socially relevant diseases like cancer through the utilization of intracellular markers and/or guide surgical procedures based on fluorescent or Raman imaging. Particularly complex probe structures have been developed within the past five years, creating a versatile toolbox for live-cell analysis, with each tool possessing its own strengths and limitations for specific studies. Analyzing the literature reports in the field, we predict that the development of ODN-based fluorescent and Raman probes will continue in the near future, disclosing novel ideas on their application in therapeutic and diagnostic strategies.
Monica-Cornelia Sardaru, Simona Morariu, Oana-Elena Carp, Elena-Laura Ursu, Alexandru Rotaru, and Mihail Barboiu
Royal Society of Chemistry (RSC)
Hybrid dextran–G-quartet dynamers produces tunable biocompatible three-dimensional thixotropic hydrogels, able to support cell growth.
Monica-Cornelia Sardaru, Irina Rosca, Cristian Ursu, Ioan-Andrei Dascalu, Elena-Laura Ursu, Simona Morariu, and Alexandru Rotaru
American Chemical Society (ACS)
Razvan Ghiarasim, Crina Elena Tiron, Adrian Tiron, Mihail-Gabriel Dimofte, Mariana Pinteala, and Alexandru Rotaru
MDPI AG
Diblock copolymers of polyhistidine are known for their self-assembly into micelles and their pH-dependent disassembly due to the amphiphilic character of the copolymer and the unsaturated imidazole groups that undergo a hydrophobic-to-hydrophilic transition in an acidic pH. This property has been largely utilized for the design of drug delivery systems that target a tumor environment possessing a slightly lower extracellular pH (6.8–7.2). The main purpose of this study was to investigate the possibility of designed poly(ethylene glycol)-polyhistidine sequences synthesized using solid-phase peptide synthesis (SPPS), to self-assemble into micelles, to assess the ability of the corresponding micelles to be loaded with doxorubicin (DOX), and to investigate the drug release profile at pH values similar to a malignant extracellular environment. The designed and assembled free and DOX-loaded micelles were characterized from a physico-chemical point of view, their cytotoxicity was evaluated on a human breast cancer cell line (MDA-MB-231), while the cellular areas where micelles disassembled and released DOX were assessed using immunofluorescence. We concluded that the utilization of SPPS for the synthesis of the polyhistidine diblock copolymers yielded sequences that behaved similarly to the copolymeric sequences synthesized using ring-opening polymerization, while the advantages of SPPS may offer facile tuning of the histidine site or the attachment of a large variety of functional molecules.
Daria Aristova, Viktoriia Kosach, Svitlana Chernii, Yuriy Slominsky, Anatoliy Balanda, Valeriy Filonenko, Sergiy Yarmoluk, Alexandru Rotaru, Hülya Gizem Özkan, Andriy Mokhir,et al.
IOP Publishing
Abstract We have studied spectral-luminescent properties of the monomethine cyanine dyes both in their free states and in the presence of either double-stranded deoxyribonucleic acids (dsDNAs) or single-stranded ribonucleic acids (RNAs). The dyes possess low fluorescence intensity in an unbound state, which is increased up to 479 times in the presence of the nucleic acids. In the presence of RNAs, the fluorescence intensity increase was stronger than that observed in the presence of dsDNA. Next, we have performed staining of live and fixed cells by all prepared dyes. The dyes proved to be cell and nuclear membrane permeant. They are photostable and brightly stain RNA-containing organelles in both live and fixed cells. The colocalization confirmed the specific nucleoli staining with anti-Ki-67 antibodies. The RNA digestion experiment has confirmed the selectivity of the dyes toward intracellular RNA. Based on the obtained results, we can conclude that the investigated monomethine cyanine dyes are useful fluorescent probes for the visualization of intracellular RNA and RNA-containing organelles such as nucleoli by using fluorescence microscopy.
Monica-Cornelia Sardaru, Irina Rosca, Simona Morariu, Elena-Laura Ursu, Razvan Ghiarasim, and Alexandru Rotaru
MDPI AG
Facile method for the preparation of β–cyclodextrin–functionalized hydrogels based on guanosine quartet assembly was described. A series of seven hydrogels were prepared by linking β–cyclodextrin molecules with guanosine moieties in different ratios through benzene–1,4–diboronic acid linker in the presence of potassium hydroxide. The potassium ions acted as a reticulation agent by forming guanosine quartets, leading to the formation of self–sustained transparent hydrogels. The ratios of the β–cyclodextrin and guanosine components have a significant effect on the internal structuration of the components and, correspondingly, on the mechanical properties of the final gels, offering a tunablity of the system by varying the components ratio. The insights into the hydrogels’ structuration were achieved by circular dichroism, scanning electron microscopy, atomic force microscopy, and X–ray diffraction. Rheological measurements revealed self–healing and thixotropic properties of all the investigated samples, which, in combination with available cyclodextrin cavities for active components loading, make them remarkable candidates for specific applications in biomedical and pharmaceutical fields. Moreover, all the prepared samples displayed selective antimicrobial properties against S. aureus in planktonic and biofilm phase, the activity also depending on the guanosine and cyclodextrin ratio within the hydrogel structure.
Elena Laura Ursu and Alexandru Rotaru
Springer International Publishing
Anda-Mihaela Craciun, Alexandru Rotaru, Corneliu Cojocaru, Ionel I. Mangalagiu, and Ramona Danac
Elsevier BV
Monica-Cornelia Sardaru, Oana Carp, Elena-Laura Ursu, Anda-Mihaela Craciun, Corneliu Cojocaru, Mihaela Silion, Vladyslava Kovalska, Ionel Mangalagiu, Ramona Danac, and Alexandru Rotaru
MDPI AG
We have designed and synthesized a series of novel, supramolecular, long-lived fluorescent probes based on the host-guest inclusion complexes formation between fluorescent indolizinyl-pyridinium salts and β-cyclodextrin. Fluorescence and electrospray ionisation mass spectrometry experiments, supported by theoretical molecular docking studies, were utilized in the monitoring of the inclusion complexes formation, evidencing the appearance of corresponding 1:1 and 1:2 species. Additionally, the influence of the guest molecule over the aggregation processes of the cyclodextrin inclusion complexes was investigated by transmission electron microscopy. The absence of cytotoxicity, cellular permeability, long-lived intracellular fluorescence, and in time specific accumulation within acidic organelles identified the investigated supramolecular entities as remarkable candidates for intracellular fluorescence probes. Co-staining experiments using specific organelle markers revealed the fact that, after a 24-h incubation period, the inclusion complexes accumulate predominantly in lysosomes rather than in mitochondria. This study opens new possibilities for a broad range of fluorescent dyes with solubility and high toxicity issues, able to form inclusion complexes with β-cyclodextrin, to be tested as intracellular fluorescence probes.
Dana Bejan, Lucian Gabriel Bahrin, Corneliu Cojocaru, Alexandru Florentin Trandabat, Narcisa Laura Marangoci, Alexandru Rotaru, and Sergiu Shova
Informa UK Limited
Abstract We report the synthesis and characterization of a two-dimensional Zn(II) coordination polymer employing a ligand with a biphenyl core containing imidazole and carboxylate groups in the presence of acetate moieties as bridging molecules. The obtained [ZnLAc]n was structurally characterized via X-ray, FTIR, TGA, PXRD, SEM and EDX analyses. Computer-aided calculations based on density functional theory (DFT) were employed to assess the optimal conformational geometries of both the starting ligand and the Zn(II) complex. Computational results were compared with the experimental data, disclosing a reasonable agreement. Comparisons between the single-crystal structures and the calculated optimized geometries of the molecular entities are discussed. In addition, the time-dependent DFT method (TD-DFT) was applied to assess the first excited state of the ligand and complex. Graphical Abstract
Elena-Laura Ursu, Gabriela Gavril, Simona Morariu, Mariana Pinteala, Mihail Barboiu, and Alexandru Rotaru
Elsevier BV
Dana Bejan, Narcisa Laura Marangoci, Alexandru Rotaru, Alexandru Florentin Trandabat, and Lucian Gabriel Bahrin
MDPI AG
2,4,6-Tris(4-iodophenyl)-1,3,5-trimethylbenzene was synthesized from 2,4,6-triphenyl-1,3,5-trimethylbenzene, using [bis(trifluoroacetoxy)iodo]benzene as the iodinating agent. The title compound was characterized by means of NMR, IR, and mass spectrometry, as well as TG analysis.
Ana-Maria Resmerita, Aurelian D. Costea, Flavian Farcas, Angela Rotaru, and Aurica Farcaș
SPIE
Poly(3,4-ethylenedioxythiophene/permethylated γ-cyclodextrin) polyrotaxane (PEDOT∙TMγCD) having bulky triphenylmethyl as stoppers was synthesized by the chemical oxidation of 3,4-ethylenedioxythiophene (EDOT) as an inclusion complex with 2,3,6-tri-O-methyl γ-cyclodextrin (TMγCD) (EDOT∙TMγCD) with a five-fold excess of iron (III) chloride oxidant over the stoichiometric amount in water. For a comparison, the reference PEDOT was synthesized under the same experimental conditions. The chemical structures of the synthesized compounds were proved by FT-IR and NMR spectroscopies. The coverage ratio of the EDOT and PEDOT backbones was found to be of 80.0 % and 43.7 %, respectively. Differential scanning calorimetry (DSC) studies of both PEDOT and PEDOT∙TMγCD samples showed no crystallization or melting peaks in the range 20-200 °C. The PEDOT∙TMγCD as dark-green powders was enough soluble in acetone, dichloromethane, CHCl3 and THF compared with those of the reference PEDOT. The optical properties of the PEDOT and PEDOT∙TMγCD compounds were investigated by UV-Vis. The UV-Vis absorption spectrum of PEDOT∙TMγCD in THF is consistent with the spectrum of the PEDOT in DMSO. Atomic force microscopy, AFM, indicated that the PEDOT∙TMγCD film is more uniformly distributed over the substrate area compared with those of the reference PEDOT. The electrochemical data provided that the investigated PEDOT∙TMγCD exhibited n- and p-doping processes. The HOMO/LUMO energy level indicates that the investigated PEDOT∙TMγCD polyrotaxane is electrochemically accessible as electron-transporting material in electronic devices.
Lucian G. Bahrin, Lilia Clima, Sergiu Shova, Irina Rosca, Corneliu Cojocaru, Dana Bejan, Monica C. Sardaru, Narcisa Marangoci, Vasile Lozan, and Alexandru Rotaru
Springer Science and Business Media LLC
Mihaela Silion, Adrian Fifere, Ana Lacramioara Lungoci, Narcisa Laura Marangoci, Sorin Alexandru Ibanescu, Radu Zonda, Alexandru Rotaru, and Mariana Pinteală
Springer International Publishing
Lucian G. Bahrin, Irina Rosca, Lilia Clima, Sergiu Shova, Dana Bejan, Alina Nicolescu, Narcisa-Laura Marangoci, Monica C. Sardaru, Vasile Lozan, and Alexandru Rotaru
Elsevier BV
Aurica Farcas, Mihaela Balan-Porcarasu, Ana-Maria Resmerita, Mihai Asandulesa, Angela Rotaru, and Flavian Farcas
SPIE
We report the effect of the macrocyclic encapsulation on the photophysical properties of poly(9,9-dioctylfluorene-alt-bithiophene) polyrotaxanes copolymers. The encapsulated compounds were synthesized by Suzuki cross-coupling reaction between 5,5'-dibromo-2,2'-bithiophene (DBT) inclusion complexes in randomly methylated β-cyclodextrin (RM-βCD), 2,3,6-tri-O-methyl β-cyclodextrin (TM-βCD), 2,3,6-tri-O-trimethylsilyl β-cyclodextrin (TMS-βCD) or cucurbit[7]uril (CB7) with a bulky 9,9-dioctylfluorene-2,7-diboronic acid bis(1,3-propanediol) ester (DF) as stoppers. These supramolecular compounds exhibited distinct improvement in the solubility, molecular weight, film forming ability, surface-morphological characteristics and reduced aggregation tendency compared to those of the neat compound. Also, the threading of conjugated backbones into macrocycles leads to an increasing environmental stability and resistance to quenching from impurities. Fluorescence emission (PL) shows vibronic transitions and a mono-exponential kinetics. The electrochemical data provided that the investigated compounds exhibited n- and p-doping processes. The encapsulation of DBT into TM-βCD or TMS-βCD cavities exhibits a greater effect on the LUMO, while the encapsulation into CB7 affects the HOMO energy levels. The HOMO/LUMO energy levels indicate that the investigated polyrotaxanes are electrochemically accessible as electron-transporting materials in electronic devices. Based on AFM analysis, polyrotaxane compounds exhibits a higher tendency to organize into fibers or linear ribbons.
Gabriela Pricope, Elena Laura Ursu, Monica Sardaru, Corneliu Cojocaru, Lilia Clima, Narcisa Marangoci, Ramona Danac, Ionel I. Mangalagiu, Bogdan C. Simionescu, Mariana Pinteala,et al.
Royal Society of Chemistry (RSC)
A novel supramolecular approach for the preparation of new non-toxic systems for staining cellular organelles is described.
Tudor Vasiliu, Corneliu Cojocaru, Alexandru Rotaru, Gabriela Pricope, Mariana Pinteala, and Lilia Clima
MDPI AG
The polyplexes formed by nucleic acids and polycations have received a great attention owing to their potential application in gene therapy. In our study, we report experimental results and modeling outcomes regarding the optimization of polyplex formation between the double-stranded DNA (dsDNA) and poly(l-Lysine) (PLL). The quantification of the binding efficiency during polyplex formation was performed by processing of the images captured from the gel electrophoresis assays. The design of experiments (DoE) and response surface methodology (RSM) were employed to investigate the coupling effect of key factors (pH and N/P ratio) affecting the binding efficiency. According to the experimental observations and response surface analysis, the N/P ratio showed a major influence on binding efficiency compared to pH. Model-based optimization calculations along with the experimental confirmation runs unveiled the maximal binding efficiency (99.4%) achieved at pH 5.4 and N/P ratio 125. To support the experimental data and reveal insights of molecular mechanism responsible for the polyplex formation between dsDNA and PLL, molecular dynamics simulations were performed at pH 5.4 and 7.4.
Elena-Laura Ursu, Florica Doroftei, Dragos Peptanariu, Mariana Pinteala, and Alexandru Rotaru
Springer Science and Business Media LLC
Alexandru Rotaru, Gabriela Pricope, Taylor N. Plank, Lilia Clima, Elena L. Ursu, Mariana Pinteala, Jeffery T. Davis, and Mihail Barboiu
Royal Society of Chemistry (RSC)
Functional G-quartet hydrogels formed from natural guanosine cross linked with benzene-1,4-diboronic acid and Mg2+ support cell growth with no visible signs of gel degradation.