Miguel Ferreira - Academia.edu (original) (raw)
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Papers by Miguel Ferreira
Contrast Media Molecular Imaging, 2013
Bioconjugate chemistry, Jan 3, 2015
The biodistribution profile of a new dextrin nanomagnetogel, which consists on γ-Fe2O3 superparam... more The biodistribution profile of a new dextrin nanomagnetogel, which consists on γ-Fe2O3 superparamagnetic nanoparticles loaded within a polymeric matrix of modified dextrin, was studied in mice. The nanomagnetogel bear a monomodal size distribution profile (average diameter 110 nm) close to neutral surface charge and higher relaxivity (r2 = 215-248 mM-1s-1 and r2/r1 = 13-11) than those of commercial formulations (r2 = 160-177 mM-1s-1 and r2/r1 = 4-7). Also the observed blood half-life - approximately 4 hours - is superior to that of similar commercially available formulations, which remain few minutes in circulation. Pegylation resulted in 1.7 and 1.2-fold lower accumulation in the liver and spleen, respectively, within the first 24 h. Noteworthy, a good correlation was obtained between the amount of polymer (quantified by scintigraphy) in the spleen, 48 h after administration, and the amount of iron physically loaded through hydrophobic interactions (quantified by ICP) indicating th...
Journal of Materials Chemistry B, 2013
This study aims at the production and characterization of a "nanomagnetogel" consisting of superp... more This study aims at the production and characterization of a "nanomagnetogel" consisting of superparamagnetic iron oxide nanoparticles (g-Fe 2 O 3) stabilized within a hydrophobized-dextrin nanogel. The nanomagnetogel obtained was extensively characterized with respect to physico-chemical (transmission electron microscopy, cryo-scanning electron microscopy, dynamic light scattering, small angle X-ray scattering), magnetic (relaxometry, MIAplex) and biocompatibility (interaction with cells) properties. The obtained nanomagnetogel formulation, with about 4 mM of iron and a diameter of 100 nm, presents relevant features as a promising magnetic resonance imaging (MRI) contrast agent, noteworthy superparamagnetic behavior, high stability, narrow size distribution and potential for magnetic guidance to target areas by means of an external magnetic field. High values of transverse relaxivity make the nanomagnetogel a promising T 2 contrast agent, allowing enhanced lesion detectability through magnetic resonance imaging. The nanomagnetogel demonstrated non-toxicity for 3T3 fibroblast cultures and was efficiently internalized by bone marrow-derived macrophages, therefore having potential as a contrast agent for MRI of the organs associated with the reticuloendothelial system (spleen, liver). The production of the nanomagnetogel is simple and easy to scale up, thus offering great technological potential.
Contrast media & molecular imaging
A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(α-amino)propionate ch... more A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(α-amino)propionate chelator is described, using the synthesis of the DO3A-N-(α-benzoylamido)propionate chelator as an illustrative example. The model Gd[DO3A-N-(α-benzoylamido)propionate] chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn(2+). The Gd[DO3A-N-(α-benzoylamido)propionate] complex is mainly excreted via the kidneys, producing a significant increase in the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its higher lipophilicity compared with Gd(DTPA). The results presented suggest that Gd[DO3A-N-(α-amido)propionate] chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents.
Dalton Transactions, 2015
Linker length has little effect on the relaxivity of Gd3+ chelates immobilized onto gold nanopart... more Linker length has little effect on the relaxivity of Gd3+ chelates immobilized onto gold nanoparticles.
Nanotechnology, 2010
The characterization of biodistribution is a central requirement in the development of biomedical... more The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a γ-emitting 153 Sm 3+ radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.
![Research paper thumbnail of Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for 68Ga PET](https://attachments.academia-assets.com/100756934/thumbnails/1.jpg)
](Dalton Transactions, 2014
A reversible pH-trigged N3O3⇆N4O2 coordination isomerism was demonstrated for the Ga[NO2A-N-(α-am... more A reversible pH-trigged N3O3⇆N4O2 coordination isomerism was demonstrated for the Ga[NO2A-N-(α-amino)propionate] chelate in the pH range 4–6.
Dalton Transactions, 2012
Gold nanoparticles functionalized with Gd 3+ chelates displaying fast water exchange, superb pH s... more Gold nanoparticles functionalized with Gd 3+ chelates displaying fast water exchange, superb pH stability and inertness towards transmetalation with Zn 2+ have been prepared and characterized as a new high relaxivity (29 mM-1 s-1 , 30 MHz, 25 ºC) Contrast Agent potentially safe for in vivo MRI applications. The Lipari-Szabo treatment for internal rotation was used to evaluate the effect of linker flexibility on the relaxivity of the gold nanoparticles. The relaxivity is limited by chelate flexibility. The effect of fast water exchange on the relaxivity of gold nanoparticles functionalized with Gd 3+ chelates is also addressed in this communication.
![Research paper thumbnail of Ln[DO3A-N-α-(pyrenebutanamido)propionate] complexes: optimized relaxivity and NIR optical properties](https://attachments.academia-assets.com/100756946/thumbnails/1.jpg)
](Dalton Trans., 2014
We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates a... more We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates are leads to targeted, high relaxivity, safe contrast agents for magnetic resonance imaging. In this work we illustrate further the expeditious nature and robustness of the synthetic methodologies developed by preparing the DO3A-N-(α-pyrenebutanamido)propionate chelator. Its Gd 3+ chelate retains the optimized water exchange, high stability and inertness of the parent complex. The pyrene moiety imparts concentration-dependent self-assembly properties and aggregation-sensitive fluorescence emission to the Gd 3+ complex. The Gd 3+ complex displays pyrene-centred fluorescence whilst the Yb 3+ and Nd 3+ complexes exhibit sensitized lanthanide-centred near-infrared luminescence. The aggregated form of the complex displays high relaxivity (32 mM −1 s −1 , 20 MHz, 25°C) thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. The relaxivity is however still limited by chelate flexibility. This report demonstrates that the DO3A-N-(α-amino)propionate chelator is a valuable platform for constructing high relaxivity CA using simple design principles and robust chemistries accessible to most chemistry labs. † Electronic supplementary information (ESI) available: Size distribution in: (a) volume (%); (b) intensity (%) for a GdL solution (5 mM, pH 7.0, 25°C) at a concentration well above the cmc (0.6 mM) (Fig. S1); temperature dependence of the water proton relaxivity for GdL (20 MHz, 1 mM, pH 6.0) (Fig. S2); pH dependence of the water proton relaxivity for GdL (20 MHz, 1 mM, 25°C) (Fig. S3); time evolution of R 1p (t)/R 1p (0) (20 MHz, pH 7.1, 25°C) for a 1.5 mM solution of GdL in 10 mM phosphate buffer without and with an equimolar amount of Zn 2+ (Fig. S4); UV-Vis spectra for the free ligand L and the GdL complex (Fig. S5); fluorescence spectra for the free ligand L in non-deoxygenated water (pH 7.0) over the concentration range 5 × 10 −5-5 × 10 −3 mol dm −3 (λ exc = 345 nm) (Fig. S6); changes in ratio excimer/monomer emission (I E /I M) for ligand L as a function of the ligand concentration (Fig. S7); best fit values for the fitting of the experimental data of I Exc /I Mono vs. [GdL] (Table S1); biodistribution of 153 SmL in Wistar rats 1 and 24 hours after i.v. injection (Table S2); equations for the analysis of 1 H NMRD and 17 O NMR data (Appendix 1
European Journal of Inorganic Chemistry, 2007
The synthesis and characterization of a new metal chelator, 4-(S)-hydroxymethyl-3,6,10-tri(carbox... more The synthesis and characterization of a new metal chelator, 4-(S)-hydroxymethyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid (H 5 EPTPACH 2 OH), is reported. Protonation constants for the ligand H 5 EPTPACH 2 OH and for the previously reported H 5 EPTPAC16 have been determined by potentiometry, which reveals that both ligands display slightly higher protonation constants relative to that of the ligand DTPA 5-. The stability constant for the [Gd(EPTPA-CH 2 OH)(H 2 O)] 2complex has also been determined by potentiometry. The obtained value (log K GdL = 16.7) is two orders of magnitude lower than that for the [Gd(EPTPA)-(H 2 O)] 2complex, which indicates the destabilizing effect of the pendant hydroxymethyl group at the EPTPA backbone. The microscopic protonation scheme has been deduced from the pH dependence of the 1 H NMR spectra of both H 5 EPTPACH 2 OH and H 5 EPTPAC16 ligands. The first two protonations occur exclusively at the backbone nitrogen atoms-the first protonation occurs preferentially at the more
Chemical Communications, 2009
We report the synthesis of a novel, versatile and easily accessible metal chelator, DO3A-N-alpha-... more We report the synthesis of a novel, versatile and easily accessible metal chelator, DO3A-N-alpha-aminopropionate, and the relaxometric characterization of its Gd(3+) complex, revealing great potential for the development of high relaxivity targeted contrast agents for magnetic resonance imaging.
European Journal of Inorganic Chemistry, 2007
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Contrast Media Molecular Imaging, 2013
Bioconjugate chemistry, Jan 3, 2015
The biodistribution profile of a new dextrin nanomagnetogel, which consists on γ-Fe2O3 superparam... more The biodistribution profile of a new dextrin nanomagnetogel, which consists on γ-Fe2O3 superparamagnetic nanoparticles loaded within a polymeric matrix of modified dextrin, was studied in mice. The nanomagnetogel bear a monomodal size distribution profile (average diameter 110 nm) close to neutral surface charge and higher relaxivity (r2 = 215-248 mM-1s-1 and r2/r1 = 13-11) than those of commercial formulations (r2 = 160-177 mM-1s-1 and r2/r1 = 4-7). Also the observed blood half-life - approximately 4 hours - is superior to that of similar commercially available formulations, which remain few minutes in circulation. Pegylation resulted in 1.7 and 1.2-fold lower accumulation in the liver and spleen, respectively, within the first 24 h. Noteworthy, a good correlation was obtained between the amount of polymer (quantified by scintigraphy) in the spleen, 48 h after administration, and the amount of iron physically loaded through hydrophobic interactions (quantified by ICP) indicating th...
Journal of Materials Chemistry B, 2013
This study aims at the production and characterization of a "nanomagnetogel" consisting of superp... more This study aims at the production and characterization of a "nanomagnetogel" consisting of superparamagnetic iron oxide nanoparticles (g-Fe 2 O 3) stabilized within a hydrophobized-dextrin nanogel. The nanomagnetogel obtained was extensively characterized with respect to physico-chemical (transmission electron microscopy, cryo-scanning electron microscopy, dynamic light scattering, small angle X-ray scattering), magnetic (relaxometry, MIAplex) and biocompatibility (interaction with cells) properties. The obtained nanomagnetogel formulation, with about 4 mM of iron and a diameter of 100 nm, presents relevant features as a promising magnetic resonance imaging (MRI) contrast agent, noteworthy superparamagnetic behavior, high stability, narrow size distribution and potential for magnetic guidance to target areas by means of an external magnetic field. High values of transverse relaxivity make the nanomagnetogel a promising T 2 contrast agent, allowing enhanced lesion detectability through magnetic resonance imaging. The nanomagnetogel demonstrated non-toxicity for 3T3 fibroblast cultures and was efficiently internalized by bone marrow-derived macrophages, therefore having potential as a contrast agent for MRI of the organs associated with the reticuloendothelial system (spleen, liver). The production of the nanomagnetogel is simple and easy to scale up, thus offering great technological potential.
Contrast media & molecular imaging
A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(α-amino)propionate ch... more A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(α-amino)propionate chelator is described, using the synthesis of the DO3A-N-(α-benzoylamido)propionate chelator as an illustrative example. The model Gd[DO3A-N-(α-benzoylamido)propionate] chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn(2+). The Gd[DO3A-N-(α-benzoylamido)propionate] complex is mainly excreted via the kidneys, producing a significant increase in the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its higher lipophilicity compared with Gd(DTPA). The results presented suggest that Gd[DO3A-N-(α-amido)propionate] chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents.
Dalton Transactions, 2015
Linker length has little effect on the relaxivity of Gd3+ chelates immobilized onto gold nanopart... more Linker length has little effect on the relaxivity of Gd3+ chelates immobilized onto gold nanoparticles.
Nanotechnology, 2010
The characterization of biodistribution is a central requirement in the development of biomedical... more The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a γ-emitting 153 Sm 3+ radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.
Dalton Transactions, 2014
A reversible pH-trigged N3O3⇆N4O2 coordination isomerism was demonstrated for the Ga[NO2A-N-(α-am... more A reversible pH-trigged N3O3⇆N4O2 coordination isomerism was demonstrated for the Ga[NO2A-N-(α-amino)propionate] chelate in the pH range 4–6.
Dalton Transactions, 2012
Gold nanoparticles functionalized with Gd 3+ chelates displaying fast water exchange, superb pH s... more Gold nanoparticles functionalized with Gd 3+ chelates displaying fast water exchange, superb pH stability and inertness towards transmetalation with Zn 2+ have been prepared and characterized as a new high relaxivity (29 mM-1 s-1 , 30 MHz, 25 ºC) Contrast Agent potentially safe for in vivo MRI applications. The Lipari-Szabo treatment for internal rotation was used to evaluate the effect of linker flexibility on the relaxivity of the gold nanoparticles. The relaxivity is limited by chelate flexibility. The effect of fast water exchange on the relaxivity of gold nanoparticles functionalized with Gd 3+ chelates is also addressed in this communication.
Dalton Trans., 2014
We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates a... more We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates are leads to targeted, high relaxivity, safe contrast agents for magnetic resonance imaging. In this work we illustrate further the expeditious nature and robustness of the synthetic methodologies developed by preparing the DO3A-N-(α-pyrenebutanamido)propionate chelator. Its Gd 3+ chelate retains the optimized water exchange, high stability and inertness of the parent complex. The pyrene moiety imparts concentration-dependent self-assembly properties and aggregation-sensitive fluorescence emission to the Gd 3+ complex. The Gd 3+ complex displays pyrene-centred fluorescence whilst the Yb 3+ and Nd 3+ complexes exhibit sensitized lanthanide-centred near-infrared luminescence. The aggregated form of the complex displays high relaxivity (32 mM −1 s −1 , 20 MHz, 25°C) thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. The relaxivity is however still limited by chelate flexibility. This report demonstrates that the DO3A-N-(α-amino)propionate chelator is a valuable platform for constructing high relaxivity CA using simple design principles and robust chemistries accessible to most chemistry labs. † Electronic supplementary information (ESI) available: Size distribution in: (a) volume (%); (b) intensity (%) for a GdL solution (5 mM, pH 7.0, 25°C) at a concentration well above the cmc (0.6 mM) (Fig. S1); temperature dependence of the water proton relaxivity for GdL (20 MHz, 1 mM, pH 6.0) (Fig. S2); pH dependence of the water proton relaxivity for GdL (20 MHz, 1 mM, 25°C) (Fig. S3); time evolution of R 1p (t)/R 1p (0) (20 MHz, pH 7.1, 25°C) for a 1.5 mM solution of GdL in 10 mM phosphate buffer without and with an equimolar amount of Zn 2+ (Fig. S4); UV-Vis spectra for the free ligand L and the GdL complex (Fig. S5); fluorescence spectra for the free ligand L in non-deoxygenated water (pH 7.0) over the concentration range 5 × 10 −5-5 × 10 −3 mol dm −3 (λ exc = 345 nm) (Fig. S6); changes in ratio excimer/monomer emission (I E /I M) for ligand L as a function of the ligand concentration (Fig. S7); best fit values for the fitting of the experimental data of I Exc /I Mono vs. [GdL] (Table S1); biodistribution of 153 SmL in Wistar rats 1 and 24 hours after i.v. injection (Table S2); equations for the analysis of 1 H NMRD and 17 O NMR data (Appendix 1
European Journal of Inorganic Chemistry, 2007
The synthesis and characterization of a new metal chelator, 4-(S)-hydroxymethyl-3,6,10-tri(carbox... more The synthesis and characterization of a new metal chelator, 4-(S)-hydroxymethyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid (H 5 EPTPACH 2 OH), is reported. Protonation constants for the ligand H 5 EPTPACH 2 OH and for the previously reported H 5 EPTPAC16 have been determined by potentiometry, which reveals that both ligands display slightly higher protonation constants relative to that of the ligand DTPA 5-. The stability constant for the [Gd(EPTPA-CH 2 OH)(H 2 O)] 2complex has also been determined by potentiometry. The obtained value (log K GdL = 16.7) is two orders of magnitude lower than that for the [Gd(EPTPA)-(H 2 O)] 2complex, which indicates the destabilizing effect of the pendant hydroxymethyl group at the EPTPA backbone. The microscopic protonation scheme has been deduced from the pH dependence of the 1 H NMR spectra of both H 5 EPTPACH 2 OH and H 5 EPTPAC16 ligands. The first two protonations occur exclusively at the backbone nitrogen atoms-the first protonation occurs preferentially at the more
Chemical Communications, 2009
We report the synthesis of a novel, versatile and easily accessible metal chelator, DO3A-N-alpha-... more We report the synthesis of a novel, versatile and easily accessible metal chelator, DO3A-N-alpha-aminopropionate, and the relaxometric characterization of its Gd(3+) complex, revealing great potential for the development of high relaxivity targeted contrast agents for magnetic resonance imaging.
European Journal of Inorganic Chemistry, 2007
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