Viviana Negri - Academia.edu (original) (raw)

Papers by Viviana Negri

Science of The Total Environment, 2022

Graphene oxide (GO) is a carbon nanomaterial used in electronics, biomedicine, environmental reme... more Graphene oxide (GO) is a carbon nanomaterial used in electronics, biomedicine, environmental remediation and biotechnology. The production of graphene will increase in the upcoming years. The carbon nanoparticles (NPs) are released into the environment and accumulated in aquatic ecosystems. Information on the effects of GO in aquatic environments and its impact on organisms is still lacking. The aim of this study was to synthesise and characterise label-free GO with controlled lateral dimensions and thickness - small GO (sGO), large GO (lGO) and monolayer GO (mlGO) - and determine their impact on Chironomus riparius, a sentinel species in the freshwater ecosystem. Superoxide dismutase (SOD) and lipid peroxidation (LPO) was evaluated after exposures for 24 h and 96 h to 50, 500, and 3000 μg/L. GOs accumulated in the gut of C. riparius and disturbed its antioxidant metabolism. We suggest that all types of GO exposure can upregulate of SOD. Moreover, both lGO and mlGO treatments caused LPO damage in C. riparius in comparison to sGO, proving its favourable lateral size impact in this organism. Our results indicate that GOs could accumulate and induce significant oxidative stress on C. riparius. This work shows new information about the potential oxidative stress of these NMs in aquatic organisms.

We report on the magnetic properties of stable suspensions from oxidized 19 Multiwalled Carbon Na... more We report on the magnetic properties of stable suspensions from oxidized 19 Multiwalled Carbon Nanotubes (MWCNT) functionalized with aminopyrene (AP). MWCNT form 20  stacking adducts with AP (AP-MWCNT), originating homogenous, stable, suspensions in 21 N,N-dimethylformamide (DMF) or melted agarose. First, we investigated the magneto-optical 22 properties of these adducts. When applying series of pulsed magnetic fields to nanotube 23 suspensions in DMF, the pattern of light dispersed increased during the magnetic pulse and 24 decreased in the intervals, a behavior consistent with magnetic field induced orientation of the 25 adducts. When adducts were suspended in a melted agarose gel under an external magnetic field, 26 the extinction coefficient of polarized light through the gel, was larger when the polarization plane 27 was parallel to the magnetic field direction. Based on the magneto-optical responses observed, we 28 further investigated the magnetic properties of AP-MWCNT im...

Aquatic Toxicology, 2019

The present of MWCNT in the digestive tract was clearly visible in exposed larvae.  This work sh... more The present of MWCNT in the digestive tract was clearly visible in exposed larvae.  This work shows the capability of MWCNT to alter the expression of genes which are involved in DNA repairing mechanisms (ATM), cell stress response (hsp27 and hsp70) and cell apoptosis.

Aquatic Toxicology, 2014

Pentachlorophenol (PCP) has been extensively used worldwide as a pesticide and biocide and is fre... more Pentachlorophenol (PCP) has been extensively used worldwide as a pesticide and biocide and is frequently detected in the aquatic environment. In the present work, the toxicity of PCP was investigated in Chironomus riparius aquatic larvae. The effects following short-and long-term exposures were evaluated at the molecular level by analyzing changes in the transcriptional profile of different endocrine genes, as well as in genes involved in the stress response and detoxification. Interestingly, although no differences were found after 12-and 24-h treatments, at 96-h exposures PCP was able to induce significant increases in transcripts from the ecdysone receptor gene (EcR), the early ecdysone-inducible E74 gene, the estrogenrelated receptor gene (ERR), the Hsp70 gene and the CYP4G gene. In contrast, the Hsp27 gene appeared to be downregulated, while the ultraspiracle gene (usp) (insect ortholog of the retinoid X receptor) was not altered in any of the conditions assayed. Moreover, Glutathione-S-Transferase (GST) activity was not affected. The results obtained show the ability of PCP to modulate transcription of different biomarker genes from important cellular metabolic activities, which could be useful in genomic approaches to monitoring. In particular, the significant upregulation of hormonal genes represents the first evidence at the genomic level of the potential endocrine disruptive effects of PCP on aquatic invertebrates.

European Journal of Radiology, 2008

Topics in Current Chemistry, 2020

Nowadays, biomaterials have become a crucial element in numerous biomedical, preclinical, and cli... more Nowadays, biomaterials have become a crucial element in numerous biomedical, preclinical, and clinical applications. The use of nanoparticles entails a great potential in these fields mainly because of the high ratio of surface atoms that modify the physicochemical properties and increases the chemical reactivity. Among them, carbon nanotubes (CNTs) have emerged as a powerful tool to improve biomedical approaches in the management of numerous diseases. CNTs have an excellent ability to penetrate cell membranes, and the sp 2 hybridization of all carbons enables their functionalization with almost every biomolecule or compound, allowing them to target cells and deliver drugs under the appropriate environmental stimuli. Besides, in the new promising field of artificial biomaterial generation, nanotubes are studied as the load in nanocomposite materials, improving their mechanical and electrical properties, or even for direct use as scaffolds in body tissue manufacturing. Nevertheless, despite their beneficial contributions, some major concerns need to be solved to boost the clinical development of CNTs, including poor solubility in water, low biodegradability and dispersivity, and toxicity problems associated with CNTs' interaction with biomolecules in tissues and organs, including the possible effects in the proteome and genome. This review performs a wide literature analysis to present the main and latest advances in the optimal design and characterization of carbon nanotubes with biomedical applications, and their capacities in different areas of preclinical research.

EDULEARN21 Proceedings, 2021

Theranostics, 2015

We describe the preparation, physico-chemical characterization and anti-inflammatory properties o... more We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1 H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1 H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery.

Chemistry - A European Journal, 2010

To design efficient targeting strategies in magnetic resonance (MR) molecular imaging application... more To design efficient targeting strategies in magnetic resonance (MR) molecular imaging applications, the formation of supramolecular adducts between (strept)avidin ((S)Av) and tribiotinylated Gd-DOTA-monoamide complexes (DOTA=1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was explored. Two compounds based on the trivalent core of tris(2-aminoethyl)amine each containing three biotin molecules and one (L1) or three (L2) DOTA-monoamide (DOTAMA) ligands were synthesized. In these tribiotinylated derivatives the biotins are spaced far enough apart to allow the formation of the supramolecular adduct with the protein and to host the chelating units in between the (S)Av layers. Size exclusion HPLC analyses indicated complete formation of very high molecular weight polymers (>2 MDa) with (S)Av in solution. A (1)H NMR spectroscopy relaxometric study on the obtained polymeric adducts showed a marked increase of the relaxivity at 35-40 MHz as a consequence of the lengthening of the tumbling time due to the formation of Gd-chelates/(S)Av polymers. The most efficient Gd(3)L2/(S)Av polymeric system was used for a test in cell cultures. The target is represented by a neural cell adhesion molecule (NCAM), which is overexpressed in Kaposi's sarcoma cells and tumor endothelial cells (TEC) and that is efficiently recognized by a biotinylated tetrameric peptide (C3d-Bio). In vitro experiments showed that only cells incubated with both C3d-Bio and Gd(3)L2/SAv polymer were hyperintense with respect to the control. Relaxation rates of cell pellets incubated with Gd(3)L2/SAv alone were not significantly different from the untreated cells demonstrating the absence of a specific binding.

Molecules, 2007

Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive de... more Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

ChemInform, 2009

Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive de... more Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

MedChemComm, 2013

We report on the preparation and characterization of magnetically oriented single-walled carbon n... more We report on the preparation and characterization of magnetically oriented single-walled carbon nanotube arrangements as novel nanoprobes to enhance anisotropically water relaxation as detected by magnetic resonance imaging methods. SWCNT suspensions immobilized in agarose gels showed evident magnetic anisotropy with significantly longer T 2 in the parallel than in the perpendicular orientations.

European Journal of Radiology, 2008

We provide a brief overview of the chemistry and most relevant properties of paramagnetic and dia... more We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T(1) and T(2) of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH(e)) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH(e), independent of water relaxivity, diffusion or exchange.

Current Topics in Medicinal Chemistry, 2011

Chemistry - A European Journal, 2010

To design efficient targeting strategies in magnetic resonance (MR) molecular imaging application... more To design efficient targeting strategies in magnetic resonance (MR) molecular imaging applications, the formation of supramolecular adducts between (strept)avidin ((S)Av) and tribiotinylated Gd-DOTA-monoamide complexes (DOTA=1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was explored. Two compounds based on the trivalent core of tris(2-aminoethyl)amine each containing three biotin molecules and one (L1) or three (L2) DOTA-monoamide (DOTAMA) ligands were synthesized. In these tribiotinylated derivatives the biotins are spaced far enough apart to allow the formation of the supramolecular adduct with the protein and to host the chelating units in between the (S)Av layers. Size exclusion HPLC analyses indicated complete formation of very high molecular weight polymers (>2 MDa) with (S)Av in solution. A (1)H NMR spectroscopy relaxometric study on the obtained polymeric adducts showed a marked increase of the relaxivity at 35-40 MHz as a consequence of the lengthening of the tumbling time due to the formation of Gd-chelates/(S)Av polymers. The most efficient Gd(3)L2/(S)Av polymeric system was used for a test in cell cultures. The target is represented by a neural cell adhesion molecule (NCAM), which is overexpressed in Kaposi's sarcoma cells and tumor endothelial cells (TEC) and that is efficiently recognized by a biotinylated tetrameric peptide (C3d-Bio). In vitro experiments showed that only cells incubated with both C3d-Bio and Gd(3)L2/SAv polymer were hyperintense with respect to the control. Relaxation rates of cell pellets incubated with Gd(3)L2/SAv alone were not significantly different from the untreated cells demonstrating the absence of a specific binding.

Angewandte Chemie International Edition, 2010

Enhanced MRI contrast has been classically induced by reducing the T 1 or T 2 relaxation rates of... more Enhanced MRI contrast has been classically induced by reducing the T 1 or T 2 relaxation rates of tissue water either through the administration of the paramagnetic complexes of DTPA or DOTA derivatives or superparamagnetic particles . More recently, the non invasive imaging of the Apparent Translational Diffusion Coefficient (ADC) of water molecules and its anisotropic orientation has been shown to provide comprehensive information on tissue microstructure and its pathologiess. However, no appropriate exogenous molecules have been designed to improve ADC contrast. An important potential exists, therefore, to increase the information content of ADC weighted Images through the use of contrast agents modifying selectively the ADC properties of tissue water. In this communication, we provide the proof of concept for this novel approach demonstrating that exogenous paramagnetic nanotubular structures induce anisotropic water diffusion detectable by MRI methods.

Science of The Total Environment, 2022

Graphene oxide (GO) is a carbon nanomaterial used in electronics, biomedicine, environmental reme... more Graphene oxide (GO) is a carbon nanomaterial used in electronics, biomedicine, environmental remediation and biotechnology. The production of graphene will increase in the upcoming years. The carbon nanoparticles (NPs) are released into the environment and accumulated in aquatic ecosystems. Information on the effects of GO in aquatic environments and its impact on organisms is still lacking. The aim of this study was to synthesise and characterise label-free GO with controlled lateral dimensions and thickness - small GO (sGO), large GO (lGO) and monolayer GO (mlGO) - and determine their impact on Chironomus riparius, a sentinel species in the freshwater ecosystem. Superoxide dismutase (SOD) and lipid peroxidation (LPO) was evaluated after exposures for 24 h and 96 h to 50, 500, and 3000 μg/L. GOs accumulated in the gut of C. riparius and disturbed its antioxidant metabolism. We suggest that all types of GO exposure can upregulate of SOD. Moreover, both lGO and mlGO treatments caused LPO damage in C. riparius in comparison to sGO, proving its favourable lateral size impact in this organism. Our results indicate that GOs could accumulate and induce significant oxidative stress on C. riparius. This work shows new information about the potential oxidative stress of these NMs in aquatic organisms.

We report on the magnetic properties of stable suspensions from oxidized 19 Multiwalled Carbon Na... more We report on the magnetic properties of stable suspensions from oxidized 19 Multiwalled Carbon Nanotubes (MWCNT) functionalized with aminopyrene (AP). MWCNT form 20  stacking adducts with AP (AP-MWCNT), originating homogenous, stable, suspensions in 21 N,N-dimethylformamide (DMF) or melted agarose. First, we investigated the magneto-optical 22 properties of these adducts. When applying series of pulsed magnetic fields to nanotube 23 suspensions in DMF, the pattern of light dispersed increased during the magnetic pulse and 24 decreased in the intervals, a behavior consistent with magnetic field induced orientation of the 25 adducts. When adducts were suspended in a melted agarose gel under an external magnetic field, 26 the extinction coefficient of polarized light through the gel, was larger when the polarization plane 27 was parallel to the magnetic field direction. Based on the magneto-optical responses observed, we 28 further investigated the magnetic properties of AP-MWCNT im...

Aquatic Toxicology, 2019

The present of MWCNT in the digestive tract was clearly visible in exposed larvae.  This work sh... more The present of MWCNT in the digestive tract was clearly visible in exposed larvae.  This work shows the capability of MWCNT to alter the expression of genes which are involved in DNA repairing mechanisms (ATM), cell stress response (hsp27 and hsp70) and cell apoptosis.

Aquatic Toxicology, 2014

Pentachlorophenol (PCP) has been extensively used worldwide as a pesticide and biocide and is fre... more Pentachlorophenol (PCP) has been extensively used worldwide as a pesticide and biocide and is frequently detected in the aquatic environment. In the present work, the toxicity of PCP was investigated in Chironomus riparius aquatic larvae. The effects following short-and long-term exposures were evaluated at the molecular level by analyzing changes in the transcriptional profile of different endocrine genes, as well as in genes involved in the stress response and detoxification. Interestingly, although no differences were found after 12-and 24-h treatments, at 96-h exposures PCP was able to induce significant increases in transcripts from the ecdysone receptor gene (EcR), the early ecdysone-inducible E74 gene, the estrogenrelated receptor gene (ERR), the Hsp70 gene and the CYP4G gene. In contrast, the Hsp27 gene appeared to be downregulated, while the ultraspiracle gene (usp) (insect ortholog of the retinoid X receptor) was not altered in any of the conditions assayed. Moreover, Glutathione-S-Transferase (GST) activity was not affected. The results obtained show the ability of PCP to modulate transcription of different biomarker genes from important cellular metabolic activities, which could be useful in genomic approaches to monitoring. In particular, the significant upregulation of hormonal genes represents the first evidence at the genomic level of the potential endocrine disruptive effects of PCP on aquatic invertebrates.

European Journal of Radiology, 2008

Topics in Current Chemistry, 2020

Nowadays, biomaterials have become a crucial element in numerous biomedical, preclinical, and cli... more Nowadays, biomaterials have become a crucial element in numerous biomedical, preclinical, and clinical applications. The use of nanoparticles entails a great potential in these fields mainly because of the high ratio of surface atoms that modify the physicochemical properties and increases the chemical reactivity. Among them, carbon nanotubes (CNTs) have emerged as a powerful tool to improve biomedical approaches in the management of numerous diseases. CNTs have an excellent ability to penetrate cell membranes, and the sp 2 hybridization of all carbons enables their functionalization with almost every biomolecule or compound, allowing them to target cells and deliver drugs under the appropriate environmental stimuli. Besides, in the new promising field of artificial biomaterial generation, nanotubes are studied as the load in nanocomposite materials, improving their mechanical and electrical properties, or even for direct use as scaffolds in body tissue manufacturing. Nevertheless, despite their beneficial contributions, some major concerns need to be solved to boost the clinical development of CNTs, including poor solubility in water, low biodegradability and dispersivity, and toxicity problems associated with CNTs' interaction with biomolecules in tissues and organs, including the possible effects in the proteome and genome. This review performs a wide literature analysis to present the main and latest advances in the optimal design and characterization of carbon nanotubes with biomedical applications, and their capacities in different areas of preclinical research.

EDULEARN21 Proceedings, 2021

Theranostics, 2015

We describe the preparation, physico-chemical characterization and anti-inflammatory properties o... more We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1 H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1 H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery.

Chemistry - A European Journal, 2010

To design efficient targeting strategies in magnetic resonance (MR) molecular imaging application... more To design efficient targeting strategies in magnetic resonance (MR) molecular imaging applications, the formation of supramolecular adducts between (strept)avidin ((S)Av) and tribiotinylated Gd-DOTA-monoamide complexes (DOTA=1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was explored. Two compounds based on the trivalent core of tris(2-aminoethyl)amine each containing three biotin molecules and one (L1) or three (L2) DOTA-monoamide (DOTAMA) ligands were synthesized. In these tribiotinylated derivatives the biotins are spaced far enough apart to allow the formation of the supramolecular adduct with the protein and to host the chelating units in between the (S)Av layers. Size exclusion HPLC analyses indicated complete formation of very high molecular weight polymers (>2 MDa) with (S)Av in solution. A (1)H NMR spectroscopy relaxometric study on the obtained polymeric adducts showed a marked increase of the relaxivity at 35-40 MHz as a consequence of the lengthening of the tumbling time due to the formation of Gd-chelates/(S)Av polymers. The most efficient Gd(3)L2/(S)Av polymeric system was used for a test in cell cultures. The target is represented by a neural cell adhesion molecule (NCAM), which is overexpressed in Kaposi's sarcoma cells and tumor endothelial cells (TEC) and that is efficiently recognized by a biotinylated tetrameric peptide (C3d-Bio). In vitro experiments showed that only cells incubated with both C3d-Bio and Gd(3)L2/SAv polymer were hyperintense with respect to the control. Relaxation rates of cell pellets incubated with Gd(3)L2/SAv alone were not significantly different from the untreated cells demonstrating the absence of a specific binding.

Molecules, 2007

Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive de... more Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

ChemInform, 2009

Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive de... more Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

MedChemComm, 2013

We report on the preparation and characterization of magnetically oriented single-walled carbon n... more We report on the preparation and characterization of magnetically oriented single-walled carbon nanotube arrangements as novel nanoprobes to enhance anisotropically water relaxation as detected by magnetic resonance imaging methods. SWCNT suspensions immobilized in agarose gels showed evident magnetic anisotropy with significantly longer T 2 in the parallel than in the perpendicular orientations.

European Journal of Radiology, 2008

We provide a brief overview of the chemistry and most relevant properties of paramagnetic and dia... more We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T(1) and T(2) of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH(e)) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH(e), independent of water relaxivity, diffusion or exchange.

Current Topics in Medicinal Chemistry, 2011

Chemistry - A European Journal, 2010

To design efficient targeting strategies in magnetic resonance (MR) molecular imaging application... more To design efficient targeting strategies in magnetic resonance (MR) molecular imaging applications, the formation of supramolecular adducts between (strept)avidin ((S)Av) and tribiotinylated Gd-DOTA-monoamide complexes (DOTA=1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was explored. Two compounds based on the trivalent core of tris(2-aminoethyl)amine each containing three biotin molecules and one (L1) or three (L2) DOTA-monoamide (DOTAMA) ligands were synthesized. In these tribiotinylated derivatives the biotins are spaced far enough apart to allow the formation of the supramolecular adduct with the protein and to host the chelating units in between the (S)Av layers. Size exclusion HPLC analyses indicated complete formation of very high molecular weight polymers (>2 MDa) with (S)Av in solution. A (1)H NMR spectroscopy relaxometric study on the obtained polymeric adducts showed a marked increase of the relaxivity at 35-40 MHz as a consequence of the lengthening of the tumbling time due to the formation of Gd-chelates/(S)Av polymers. The most efficient Gd(3)L2/(S)Av polymeric system was used for a test in cell cultures. The target is represented by a neural cell adhesion molecule (NCAM), which is overexpressed in Kaposi's sarcoma cells and tumor endothelial cells (TEC) and that is efficiently recognized by a biotinylated tetrameric peptide (C3d-Bio). In vitro experiments showed that only cells incubated with both C3d-Bio and Gd(3)L2/SAv polymer were hyperintense with respect to the control. Relaxation rates of cell pellets incubated with Gd(3)L2/SAv alone were not significantly different from the untreated cells demonstrating the absence of a specific binding.

Angewandte Chemie International Edition, 2010

Enhanced MRI contrast has been classically induced by reducing the T 1 or T 2 relaxation rates of... more Enhanced MRI contrast has been classically induced by reducing the T 1 or T 2 relaxation rates of tissue water either through the administration of the paramagnetic complexes of DTPA or DOTA derivatives or superparamagnetic particles . More recently, the non invasive imaging of the Apparent Translational Diffusion Coefficient (ADC) of water molecules and its anisotropic orientation has been shown to provide comprehensive information on tissue microstructure and its pathologiess. However, no appropriate exogenous molecules have been designed to improve ADC contrast. An important potential exists, therefore, to increase the information content of ADC weighted Images through the use of contrast agents modifying selectively the ADC properties of tissue water. In this communication, we provide the proof of concept for this novel approach demonstrating that exogenous paramagnetic nanotubular structures induce anisotropic water diffusion detectable by MRI methods.