Raluca M Fratila

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Verified

Raluca verified their affiliation via an institutional email.

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• PhD
• Tenured Scientist at Spanish National Research Council

Rationale: The cardiac scar is an area rich in collagen. It is populated by myofibroblasts and lacks Connexin 43 expressing cardiomyocytes. Myocardial infarctions have so far proven little amenable to gene- and cell-based therapeutic interventions. Our aim was to establish an experimental approach with translational potential for effective cell-bas...

A collection of magnetic nanoparticles with average particle sizes in the range between 9 and 78 nm were prepared using several synthetic approaches that also rendered different particle morphologies (spherical,...

In this work, we report the disruptive use of membrane-localized magnetic hyperthermia to promote the internalization of cell-impermeant probes (fluorescent molecules and small interfering RNA), without affecting cell viability.

Heating magnetic nanoparticles (MNPs) with AC (Alternating Current) magnetic fields has received significant attention in recent years, particularly for biomedical uses. However, most studies focus on characterizing the heat release, overlooking the fact that the MNPs in the viscous cell environment constitute a dynamic magnetic colloid whose confi...

The cardiac scar is a collagen-rich area, which is populated by myofibroblasts and has proven little amenable for therapeutic interventions. Herein, we have established an efficient targeting strategy for cardiac lesions by genetically manipulating embryonic cardiac myofibroblasts (mFB) in vitro , load the cells with magnetic nanoparticles and inje...

Oriented and covalent immobilization of proteins on magnetic nanoparticles (MNPs) is particularly challenging as it requires both the functionality of the protein and the colloidal stability of the MNPs to be preserved. Here, we describe a simple, straightforward, and efficient strategy for MNP functionalization with proteins using metal affinity b...

En este artículo se introducen los conceptos de química “click” y química bioortogonal, que han recibido el Premio Nobel de Química 2022 por sus numerosas ventajas (sencillez, robustez, rendimientos prácticamente cuantitativos, etc.). Se describen en detalle las principales reacciones bioortogonales, las cuales se pueden llevar a cabo en sistemas v...

In this work, we report the use of bioorthogonal chemistry, specifically the strain-promoted click azide-alkyne cycloaddition (SPAAC) for the covalent attachment of magnetic nanoparticles (MNPs) on living cell membranes. Four types of MNPs were prepared, functionalized with two different stabilizing/passivation agents (a polyethylene glycol derivat...

The simultaneous detection and quantification of several iron-containing species in biological matrices is a challenging issue. Especially in the frame of studies using magnetic nanoparticles for biomedical applications, no gold-standard technique has been described yet and combinations of different techniques are generally used. In this work, AC m...

During the last decade, the possibility to remotely control intracellular pathways using physical tools has opened the way to novel and exciting applications, both in basic research and clinical applications. Indeed, the use of physical and non-invasive stimuli such as light, electricity or magnetic fields offers the possibility of manipulating bio...

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns...

Magnetic hyperthermia (MH) was used to treat a murine model of pancreatic cancer. This type of cancer is generally characterized by the presence of dense stroma that acts as a barrier for chemotherapeutic treatments. Several alternating magnetic field (AMF) conditions were evaluated using three-dimensional (3D) cell culture models loaded with magne...

Bioorthogonal chemistry comprises chemical reactions that can take place inside complex biological environments, providing outstanding tools for the investigation and elucidation of biological processes. Its use in combination with nanotechnology can lead to further developments in diverse areas of biomedicine, such as molecular bioimaging, targete...

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo up...

Magnetic hyperthermia is a cancer treatment based on the exposure of magnetic nanoparticles to an alternating magnetic field in order to generate local heat. In this work, 3D cell culture models were prepared to observe the effect that a different number of internalized particles had on the mechanisms of cell death triggered upon the magnetic hyper...

Isolated iron oxide magnetic nanoparticles (MNPs), 12 nm in diameter, coated with oleic acid molecules as capping agents have been deposited by the Langmuir-Blodgett (LB) method onto a model cell membrane incorporating 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and Cholesterol (Chol) in the 1:1 ratio, which was also fabricated by the LB tec...

Nanomaterials for Magnetic and Optical Hyperthermia Applications focuses on the design, fabrication and characterization of nanomaterials (magnetic, gold and hybrid magnetic-gold nanoparticles) for in vitro and in vivo hyperthermia applications, both as standalone and adjuvant therapy in combination with chemotherapy. The book explores the potentia...

Magnetic hyperthermia is a promising therapy for the localized treatment of cancer based on the exposure of magnetic nanoparticles to an external alternating magnetic field. In order to evaluate some of the mechanisms involved in the cellular damage caused by this treatment, two different 3D cell culture models were prepared using collagen, which i...

Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and m...

Silver nanoparticles have particular properties that contribute to their very promising applications, novel in various fields of science, such as the development of biosensors, the diagnosis and treatment of cancer, the controlled release of drugs and the antimicrobial potential. The biological synthesis of nanoparticles is of great interest over o...

To improve the selectivity of magnetic nanoparticles for tumor treatment by hyperthermia, Fe3O4 nanoparticles have been functionalized with a peptide of the type arginine-glycine-aspartate (RGD) following a “click” chemistry approach. The RGD peptide was linked onto the previously coated nanoparticles in order to target αvβ3 integrin receptors over...

Protein corona formed on the surface of nanoparticle in biological medium determines its behavior in vivo. Here, iron oxide nanoparticles containing the same core and shell, but bearing two different surface coatings, either glucose or poly(ethylene glycol), were evaluated. The nanoparticles protein adsorption, in vitro degradation, and in vivo bio...

Herein we report the synthesis of “clickable” magnetic nanoparticles (MNPs) stable in suspension in physiological media for bioorthogonal click chemistry applications. The MNPs incorporate in their coating a cyclooctynyl derivative for strain-promoted azide-alkyne (SPAAC) cycloaddition and either a polyethylene glycol or a glucose moiety to ensure...

A highly sensitive and selective ratiometric sensor for the quantification of cyanide (CN⁻) in aqueous samples has been developed using spherical gold nanoparticles (AuNPs) stabilized by polysorbate 40 (PS-40). Three different AuNP sizes (14, 40 and 80 nm mean diameters) were used to evaluate the response of the sensor using both colorimetric and R...

BACKGROUND AND OBJECTIVES: To determine prognosis and treatment, accurate nodal staging is essential in many tumor types. After injection of clinical grade superparamagnetic iron oxide (SPIO) nanoparticles, it has been shown that metastatic lymph nodes can be distinguished from benign specimens using MR imaging. However, MR does not benefit per-ope...

Conventional methods to determine the kinetic parameters for a certain reaction require multiple, separate isothermal experiments resulting in time and material-consuming processes. Here, an approach to determine the kinetic information within a single non-isothermal on-flow experiment is presented, consuming less than ten micromoles of reagents an...

In this critical review we discuss the most recent advances in the field of biosensing applications of magnetic glyconanoparticles. We first give an overview of the main synthetic routes to obtain magnetic-nanoparticle–carbohy- drate conjugates and then we highlight their most promising applications for magnetic relaxation switching sensing, cell a...

High aspect ratio magnetic nanomaterials possess anisotropic properties that make them attractive for biological applications. Their elongated shape enables multivalent interactions with receptors through the introduction of multiple targeting units on their surface, thus enhancing cell internalization. Moreover, due to their magnetic anisotropy, h...

Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional (3D) scaffolds for regenerative medicine and clinical purposes. This is even more important when multipotent human bone marrow stromal cells (hMSCs) are used, as it could offer a method to understand in real time the dyna...

This study describes that the current rectification ratio, (R ≡ |J|(-2.0 V)/|J|(+2.0 V) for supramolecular tunneling junctions with a top-electrode of eutectic gallium indium (EGaIn) that contains a thin (0.7 nm) supporting outer oxide layer (Ga2O3), increases by up to four orders of magnitude when voltage pulses of > +1.0 V up to +2.5 V are applie...

The field of nanotechnology applied to medicine (nanomedicine) is developing at a fast pace and is expected to provide solutions for early diagnosis, targeted therapy and personalized medicine. However, designing nanomaterials for biomedical applications is not a trivial task. Avoidance of the immune system, stability in physiological media, contro...

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique, but its low sensitivity and highly sophisticated, costly, equipment severely constrain more widespread applications. Here we show that a non-resonant planar transceiver microcoil integrated in a microfluidic chip (detection volume 25 nl) can detect different nuclides...

Accessing 1,2,3-triazole compounds through the copper-catalysed azide–alkyne ‘‘click’’ cycloaddition reaction is now a routine synthetic tool which has resulted in a huge amount of novel molecules of varied complexity bearing such heterocycles. 3-N-Alkyl-1,2,3-triazolium salts constitute an example of ‘‘post-click’’ chemistry arising from the ‘‘cli...

The ability to accurately detect tumor metastases in lymph nodes is essential for intra-operative staging of various malignancies. Histopathological assessment of nodes has the drawback of a time delay before results are available to the surgeon and a likelihood of missing metastases. Photoacoustic (PA) imaging has been shown to possess the potenti...

The synthesis of three families of sialyl LewisX (sLeX) mimetics based on triazole and bis-triazole scaffolds is reported. The flexibility of these mimetics is dictated by the scaffold and gradually increases from flexible to rigid. All three families were accessible by straightforward synthetic routes and by taking advantage of the unique features...

Biomaterials with surface antibacterial properties are promising components for medical implants that might provide an alternative to conventional systemic antibiotic treatments. Herein is reported a general method, based on plasma polymerization techniques, to promote the formation of ‘‘clickable surfaces’’ which can be conjugated with chemically...

Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value...

Detection of tumor metastases in the lymphatic system is essential for accurate staging of malignancies. Commercially available superparagmagnetic nanoparticles (SPIOs) accumulate in normal lymph tissue after injection at a tumor site, whereas less or no accumulation takes place in metastatic nodes, thus enabling lymphatic staging using MRI. We ver...

The invention relates to a Nuclear Magnetic Resonance (NMR) spectroscopy device adapted for carrying out 1D and nD homo- and heteronuclear NMR spectroscopy measurements of a plurality of nuclei, comprising an RF coil adapted to transmit RF to and/or receive RF from a measuring volume, wherein the RF coil forms part of a non-tuned radiofrequency cir...

Detection of tumor metastases in the lymphatic system is essential for accurate staging of malignancies. Commercially available superparagmagnetic nanoparticles (SPIOs) accumulate in normal lymph tissue after injection at a tumor site, whereas less or no accumulation takes place in metastatic nodes, thus enabling lymphatic staging using MRI. We ver...

A new method for selecting sentinel lymph nodes (SNs) in colo-rectal cancer tissue was investigated in 12 patients. A tracer consisting of superparamagnetic ironoxide (SPIO) nanoparticles was injected in the re-sected tissue. A handheld magnetic probe was used to select SNs to which the SPIO was drained. Vibrating sample magnetometry was per-formed...

While analytical methods sensitive to very small amounts have been in use for many years, in the field of NMR spectroscopy there is still an intrinsic lack of sensitivity when dealing with small amounts of material. With time, differents approaches were used to improve the signal-to-noise ratio (SNR) of the experiments. The improvement of microcoil...

Photoacoustic detection of superparamagnetic iron oxide nanoparticles was performed in resected rat lymph nodes opening up possibilities for intra-operative nodal staging in oncology.

Mesoionic 4,4'-bis(1,2,3-triazole-5,5'-diylidene) Rh(I) complexes having a C2 chiral 4,4'-axis were accessed from 3-alkyltriazolium salts in virtually complete de. Their structure and configurational integrity were assessed by NMR spectroscopy, X-ray crystallography, and chiral HPLC. Computational analysis of the MICs involved in the reaction sugge...

Copper-catalyzed cycloaddition of ethynyltriazoles (I) with azides provides precursors (III) which can be converted into title compounds as shown for (IIIb).

A new method for selecting sentinel lymph nodes (SNs) in colorectal cancer tissue was investigated in 12 patients. A tracer consisting of superparamagnetic ironoxide (SPIO) nanoparticles was injected in the resected tissue. A handheld magnetic probe was used to select SNs to which the SPIO was drained. Vibrating sample magnetometry was performed on...

The synthesis of 2-(arylaminomethyl)phenylboronic acid via an amination–reduction reaction has been investigated within a model system comprising 2-formylphenylboronic acid and N-ethylaniline. Adoption of the appropriate reaction conditions influences the reactivity of 2-formylphenylboronic acid, enabling efficient synthesis of so-far unobtainable...

Nonsymmetrically substituted 4,4'-bis(1,2,3-triazolium) salts were prepared in a totally site-specific manner by copper(I)-catalyzed ‘click’ [2+3] cycloaddition of 3-alkyl-4-ethynyl-1,2,3-triazolium salts with alkyl and aryl azides. Competition experiments demonstrated that triazolium alkynes were more reactive than their triazole counterparts in C...

Locally applied antibiotics under temporally controlled release present many advantages over systemic clinical treatments, e.g. efficiency and side effects. This can be achieved by a coating on top of the medical device, in which the antibiotic is stored. This study presents the use of plasma polymerization to produce such a coating using N,O-bis-t...

Herewith we present the use of an NMR-chip (rf-planar microcoil integrated on top of a glass substrate) for rapid reaction optimization of continuous-flow microwave-assisted chemical processes. Monitoring reactions under microwave irradiation with the aim of optimizing the reaction conditions is a complex task. Traditional methods are not adequate...

Nur 23 Enzymmoleküle genügen einem Bioassay, der auf dem Wechselspiel zwischen multivalenten und monovalenten supramolekularen Wechselwirkungen beruht: Ein Diferrocenyl-Ligand (rot) bewirkt die Bildung von Gold-Nanopartikelclustern, nach der Oxidation des Liganden wird bevorzugt ein konkurrierendes monovalentes Gastmolekül (blau) gebunden und das A...

Five members ring derivatives represent an important group of organic compounds, many of them exhibit significant biological activity, including anti-rheumatic agents such as antipyrine and leflunomide (Arava). Due to the foretold importance of these products, our approach aims to be a continuous-flow system 1 that would allow us to monitorize and...

RGD peptidomimetics touch DNA: A few RGD cyclic peptidomimetics, each incorporating a densely substituted β-lactam moiety, were prepared, and their effect on extracellular adhesion and intracellular gene regulation through αVβ3 integrin was studied in human endothelial cells (HUVECs). Surprisingly, the cyclic tetrapeptide with a deleted glycine res...

The improvement of microcoil NMR probes for the analysis of mass-limited and volume-limited samples may be nowadays one of the closest attempts to finally achieve the intrinsic sensitivity of NMR. As the signal-to-noise ratio (SNR) improves when the filling factor is optimal, our approach undertakes the use of a microfluidic system to achieve a clo...

Nuclear magnetic resonance (NMR) spectroscopy is one of the most information-rich analytical techniques available. However, it is also inherently insensitive, and this drawback precludes the application of NMR spectroscopy to mass- and volume-limited samples. We review a particular approach to increase the sensitivity of NMR experiments, namely the...

Conformationally restricted NADH peptidomimetics 4a–e, characterized by the presence of a (1,4-dihydronicotinamide)-(β-lactam) moiety, have been synthesized and used to study the Mg2+ cation-promoted asymmetric reduction of alkyl aroylformates in acetonitrile. Increasing the bulkiness of peripheral substituents at the nitrogen atom of the β-lactam...

Unsymmetrically 1,1'-disubstituted 4,4'-bis-1H-1,2,3-triazoles 4 have been prepared from 4-ethynyl-1,2,3-triazoles 5 and azides. Following a "double-click" strategy, two complementary approaches were implemented for the preparation of the key 4-ethynyltriazole intermediates 5: (a) the stepwise Swern oxidation/Ohira-Bestman alkynylation of readily a...

Mechanistic details of the Mg(2+) ion-activated enantioselective reduction of methyl benzoylformate have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a beta-lactam ring. Computation of the reaction pathway revealed important structural differences between the intermediate NADH/Mg(2+)/ArCOCO(2)R terna...

Ring opening of alpha-substituted-alpha-methoxycarbonyl-N-nosylaziridines provides a practical access to enantiopure alpha,alpha'-disubstituted beta-lactam scaffolds, novel types of ditopic reverse turn surrogates. The procedure is general, short, and high yielding and starts from handy alpha-substituted serinates and alpha-amino acid derivatives.

Latent acidity of alpha-alkyl-alpha-amino-N-[(silyl)methyl]-beta-lactams enabled a concise entry to lithium nonenolate N-methyl-azetidinone carbanions lithiated alpha' to the beta-lactam nitrogen, owing to the stabilizing "alpha-effect" of one or two trimethylsilyl groups. (n)BuLi/TMEDA and (t)BuLi/TMEDA were the bases of choice for complete deprot...

The synthesis of succinimidyl ester of 4,7diphenyl-1,2,5-oxadiazolo[3,4-c]pyridine-6-carboxylic acid (DOPC) led to a new, fluorescent, amine-specific reagent, in a good yield. The efficiency of DOPC-ester in protein labeling was evidenced using bovine serum albumin (BSA) as a proteic target. The labeled BSA thus obtained is optimally excited within...

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochemical determinant of the alpha-alkylation reaction in beta-branched alpha-phenyloxazolidinyl- or alpha-diphenyloxazolidinyl-beta-lactams and provides the first stereocontrolled access to syn-alpha-amino-alpha,beta-dialkyl(aryl)-beta-lactams. These products are readily transfo...

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochem. determinant of the alpha-alkylation reaction in beta-branched alpha-phenyloxazolidinyl- or alpha-diphenyloxazolidinyl-beta-lactams and provides the first stereocontrolled access to syn-alpha-amino-alpha,beta-dialkyl(aryl)-beta-lactams, e.g. I. These products are readily tr...

Novel enantiopure (i)-(β-lactam)-(Gly)-(i+3) peptide models, defined by the presence of a central α-alkyl-α-amino-β-lactam ring placed as the (i+1) residue, have been synthesized in a totally stereocontrolled way by α-alkylation of suitable N-[bis(trimethylsilyl)methyl]-β-lactams. The structural properties of these β-lactam pseudopeptides have been...

Luminescent materials can be found in a broad range of daily applications, such as cathode ray tubes, projection televisions, fluorescent tubes, light emitting diodes, and X-ray detectors. Among different forms of luminescence our research group is focused on synthesis of new electroluminescent organic materials. We want to report the dehydration o...