Biomedical Applications of Iron Oxide Nanoparticles: Current Insights Progress and Perspectives

The enormous development of nanomaterials technology and the immediate response of many areas of science, research, and practice to their possible application has led to the publication of thousands of scientific papers, books, and reports. This vast amount of information requires careful classification and order, especially for specifically targeted practical needs. Therefore, the present review aims to summarize to some extent the role of iron oxide nanoparticles in biomedical research. Summarizing the fundamental properties of the magnetic iron oxide nanoparticles, the review’s next focus was to classify research studies related to applying these particles for cancer diagnostics and therapy (similar to photothermal therapy, hyperthermia), in nano theranostics, multimodal therapy. Special attention is paid to research studies dealing with the opportunities of combining different nanomaterials to achieve optimal systems for biomedical application. In this regard, original data about the synthesis and characterization of nanolipidic magnetic hybrid systems are included as an example. The last section of the review is dedicated to the capacities of magnetite-based magnetic nanoparticles for the management of oncological diseases.Fil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Martín, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Otarola, Jessica Johana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Vakarelska, Ekaterina. University of Sofia; BulgariaFil: Simeonov, Vasil. University of Sofia; BulgariaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Nedyalkova, Miroslava. University of Sofia; Bulgari

Gd(OH)3 as Modifier of Iron Oxide Nanoparticles—Insights on the Synthesis, Characterization and Stability

Magnetic resonance imaging is one of the most widely used diagnostic techniques, since it is non-invasive and provides high spatial resolution. Contrast agents (CAs) are usually required to improve the contrast capability. CAs can be classified as T1 (or positive) or T2 (or negative) contrast agents. Nowadays, gadolinium chelates (which generate T1 contrast) are the most used in clinical settings. However, the use of these chelates presents some drawbacks associated with their toxicity. Iron oxide magnetic nanoparticles (MNPs) have been extensively investigated as CA for MRI, especially for their capacity to generate negative contrast. The need for more efficient and safer contrast agents has focused investigations on the development of dual CAs, i.e., CAs that can generate both positive and negative contrast with a single administration. In this sense, nanotechnology appears as an attractive tool to achieve this goal. Nanoparticles can be modified not only to improve the contrast ability of the current CAs but also to enhance their biocompatibility, resolving toxicity issues. With the aim of contributing to the field of development of dual T1/T2 contrast agents for MRI, here, we present the obtained results of the synthesis of hybrid nanoparticles composed of magnetite/maghemite and gadolinium hydroxide. Exhaustive characterization work was conducted in order to understand how the hybrid nanoparticles were formed. The nanoparticles were extensively characterized through FTIR and UV?Vis spectroscopy, TEM and SEM microscopy, X-ray diffraction (XRD) analysis, dynamic light scattering, zeta potential, thermogravimetric analysis, energy-dispersive X-ray and vibrating-sample magnetometry. Stabilization studies were carried out to get an idea of the behavior of nanohybrids in physiological media. Special interest was given to the evaluation of Gd3+ leaching. It was found that carbohydrate coating as well as the adsorption of proteins on the surface may improve the stabilization of hybrid nanoparticles.Fil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Rivero, Paula Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Muñoz Medina, Guillermo Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Sanchez, Francisco Homero. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

The synthesis of C2 symmetry diesters of (3R,4R)-TTFOL through a green and stereoselective (2R,3R)-TADDOL rearrangement

An efficient, green, and atom economic methodology for the stereoselective synthesis of C2 symmetry (3R,4R)-TTFOL diester derivatives has been developed. The procedure occurs through a (2R,3R)-TADDOL dioxolane cleavage and rearrangement under mild conditions by its reaction with a carboxylic acid in the presence of TFAA/H3PO4 without the need for an inert atmosphere to give generally high yields.Fil: Costantino, Andrea Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Galmádez, Antonio. Universidad de Chile; ChileFil: Ocampo, Romina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Mandolesi, Sandra Delia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Koll, Liliana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Efficient routes to racemic and enantiomerically pure (S)-BINOL diesters

A systematic study for esterification procedures to the synthesis of BINOL diesters is described. Reaction conditions with TFAA and 85% H3PO4 were selected as the best procedure to prepare enantiomerically pure (S)-BINOL diesters VIII to XI with almost quantitative yields and very low reaction times.Fil: Costantino, Andrea Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; ArgentinaFil: Ocampo, Romina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; ArgentinaFil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; ArgentinaFil: Fernandez, Gustavo Adrian. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Koll, Liliana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; ArgentinaFil: Mandolesi, Sandra Delia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur. Fundacion de la Universidad Nacional del Sur; Argentin

Nanotechnology in Veterinary Sciences: Magnetic nanosystems development based in fu

Las nanopartículas magnéticas (NPMs) a base de magnetita (Fe3O4) recubiertas con sílica encuentran diversas aplicaciones en el campo de la nanotecnología biomédica, debido a su estabilidad en medio acuoso. Sin embargo, la inercia de la sílica en cuanto a su reactividad limita la incorporación de funcionalizantes específicos como fármacos y otros ligandos de interés. El desafío de este trabajo se centra en obtener NPMs biocompatibles recubiertas con sílica y gelatina para ser aplicadas como agentes teranósticos en diversos campos biomédicos, incluso en medicina veterinaria. La terapia fotodinámica representa una alternativa y un complemento a la quimio y radioterapia, herramientas convencionales para el tratamiento de diferentes patologías como las oncológicas. Consiste en la utilización de moléculas fotosensibles que, al ser activadas con luz de una determinada longitud de onda, transfieren su exceso de energía a moléculas de oxígeno vecinas. Este fenómeno genera especies reactivas de oxígeno tóxicas para las células. De este modo, la incorporación de un agente fotosensible a las NPMs de sílica funcionalizadas con gelatina facilitaría su transporte específico hacia las células afectadas a partir del efecto de un campo magnético externo. Esto resultaría en un teranóstico funcional tanto para el diagnóstico (mediante RMI) como para el tratamiento (fototerapia). En este trabajo se exploraron diversas condiciones experimentales a partir de NPMs de magnetita recubierta con ácido cítrico y sílica para la deposición de gelatina a partir del método de co-precipitación. Se obtuvo una formulación óptima que fue caracterizada integralmente desde el punto de vista fisicoquímico. Como molécula fotosensible se seleccionó al azul de metileno (AM) y se exploraron dos vías para su incorporación a las NPMs: 1-adsorción simple durante 24 horas y 2-encapsulamiento. La evaluación de ambos procedimientos reveló la incorporación exitosa del agente fotosensible, obteniéndose nanosistemas magnéticos con potenciales propiedades teranósticas aplicables en el campo veterinario.Fil: Agotegarary, Mariela Alejandra. Universidad Nacional del Sur. Departamento de Química; ArgentinaFil: Andreocci, Emanuel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Kudra, Duska. Universidad de Banka Luka; Bosnia y HerzegovinaFil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Selective contrast agents with potential to the earlier detection of tumors: Insights on synthetic pathways, physicochemical properties and performance in MRI assays

Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T2 contrast agent. The T2- weighted images obtained as well as the calculated r2, indicated that MNPs-AA could act as efficient T2 contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the cellular function neither exert cytotoxicity using the three explored doses. The internalization of the nanoparticles on the cellular structure was confirmed quanti and qualitatively using atomic absorption spectroscopy and Prussian blue techniques respectively. From these results, it emerges that ascorbic acid coated-magnetite nanoparticles may be used as alternative contrast agent to avoid or minimize some toxicological issues related to the widely used gadolinium.Instituto de Física La Plat

Selective contrast agents with potential to the earlier detection of tumors: Insights on synthetic pathways, physicochemical properties and performance in MRI assays

Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T2 contrast agent. The T2- weighted images obtained as well as the calculated r2, indicated that MNPs-AA could act as efficient T2 contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the cellular function neither exert cytotoxicity using the three explored doses. The internalization of the nanoparticles on the cellular structure was confirmed quanti and qualitatively using atomic absorption spectroscopy and Prussian blue techniques respectively. From these results, it emerges that ascorbic acid coated-magnetite nanoparticles may be used as alternative contrast agent to avoid or minimize some toxicological issues related to the widely used gadolinium.Instituto de Física La Plat

Selective contrast agents with potential to the earlier detection of tumors: Insights on synthetic pathways, physicochemical properties and performance in MRI assays

Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T2 contrast agent. The T2- weighted images obtained as well as the calculated r2, indicated that MNPs-AA could act as efficient T2 contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the cellular function neither exert cytotoxicity using the three explored doses. The internalization of the nanoparticles on the cellular structure was confirmed quanti and qualitatively using atomic absorption spectroscopy and Prussian blue techniques respectively. From these results, it emerges that ascorbic acid coated-magnetite nanoparticles may be used as alternative contrast agent to avoid or minimize some toxicological issues related to the widely used gadolinium.Fil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Martin, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Coral, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Institución Universitaria CESMAG; ColombiaFil: Muraca, Diego. Universidade Estadual de Campinas; BrasilFil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Magnetic iron oxide nanoparticles as novel and efficient tools for atherosclerosis diagnosis

Cardiovascular complications derivate from atherosclerosis are the main cause of death in western world. An early detection of vulnerable atherosclerotic plaques is primordial for a better care of patients suffering the pathology. In this context nanotechnology has emerged as a promising tool to achieve this goal. Nanoparticles based on magnetic iron oxide (MNPs) have been extensively studied in cardiovascular diseases diagnosis, as well as in the treatment and diagnostic of other pathologies. The present review aims to describe and analyze the most current literature regarding to this topic, offering the level of detail required to reproduce the experimental tasks providing a critical input of the latest available reports. The current diagnostic features are presented and compared, highlighting their advantages and disadvantages. Information on novel technology intended to this purpose is also recompiled and in deep analyzed. Special emphasis is placed in magnetic nanotechnology, remarking the possibility to assess selective and multifunctional systems to the early detection of artherosclerotic pathologies. Finally, in view of the state of the art, the future perspectives about the trends on MNPs in artherosclerorsis diagnostic and treatment have also been addressed.Fil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Stimuli-responsive nanotheranostics intended for oncological diseases: In vitro evaluation of their target, diagnostic and drug release capabilities.

Magnetic nanotheranostics were designed from iron oxide nanoparticles functionalized with folic acid (FA) and loaded with doxorubicin (Doxo) as a therapeutic agent. The incorporation of Doxo was carefully examined to attain a satisfactory drug loading efficiency. The magnet-guiding ability was examined in vitro. To achieve this, a novel continuous flow system was fabricated to quantify the amount of MNPs retained in the magnet site in an environment and under conditions mimicking the bloodstream. The obtained data suggest that almost 21% of the total circulating nanoparticles accumulated in the target site after 45 min of assay. Such amount ensured the doses of Doxo commonly employed during in vivo studies. The release of Doxo was analysed by implementing an original procedure devoted to simulate the pathways followed by MNPs once intravenously administered. From these studies, reliable data on the amount of drug that effectively reached the target site were obtained. The efficiency of the nanosystems as selective contrast agents in MRI was analysed using clinical 1.5 T equipment. Their potential as T2 weighted contrast media was demonstrated. The data collected within this work appear as the former initial stage to validate the nanotheranostics before in vivo evaluation of this novel technology.Fil: Azcona, Pamela Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Grunhut, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin