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1.
Molecules ; 28(19)2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37836718

RESUMEN

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 µg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1-10 µg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.


Asunto(s)
Nanopartículas , Terapia de Protones , Animales , Ratones , Protones , Terapia de Protones/métodos , Zinc/farmacología , Nanopartículas Magnéticas de Óxido de Hierro
2.
Nanomedicine ; 17: 26-35, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30654185

RESUMEN

The importance of atherosclerosis is driving research to create improved diagnostic tools based on molecular imaging. Pretargeted imaging is the use of bioorthogonal probes that selectively accumulate upon reaction with a pre-modified biomolecule in vivo. To date, this very promising approach has not been applied to atherosclerosis. Neither has been the use of a single nano-radiomaterial for PET / T1-MR imaging of atherosclerosis. Here, we synthesized bioorthogonal nano-radiomaterials for in vivo pretargeted molecular imaging in a mouse model of atherosclerosis. Based on tetrazine-ligation, these functionalized 68Ga iron oxide nano-radiomaterials provide simultaneous PET and T1-MRI signals and selectively accumulate in atherosclerotic plaques in mice sequentially injected with trans-cyclooctene-modified antibodies against oxidized LDL followed by the hybrid nano-radiomaterial. Our results demonstrate the ability of this approach to unambiguously detect atherosclerosis. Furthermore, we show the first example of how hybrid imaging can be used for pretargeted bioorthogonal molecular imaging with nanomaterials.


Asunto(s)
Aterosclerosis/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Animales , Compuestos Férricos/análisis , Radioisótopos de Galio/análisis , Imagen por Resonancia Magnética/métodos , Ratones Endogámicos C57BL , Modelos Moleculares , Imagen Molecular/métodos , Nanoestructuras/análisis , Tomografía de Emisión de Positrones/métodos
3.
Molecules ; 24(7)2019 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-30925778

RESUMEN

Here, we present a comprehensive review on the use of microwave chemistry for the synthesis of iron-oxide nanoparticles focused on molecular imaging. We provide a brief introduction on molecular imaging, the applications of iron oxide in biomedicine, and traditional methods for the synthesis of these nanoparticles. The review then focuses on the different examples published where the use of microwaves is key for the production of nanoparticles. We study how the different parameters modulate nanoparticle properties, particularly for imaging applications. Finally, we explore principal applications in imaging of microwave-produced iron-oxide nanoparticles.


Asunto(s)
Compuestos Férricos/síntesis química , Microondas , Imagen Molecular/métodos , Nanopartículas/química , Animales , Medios de Contraste/química , Humanos , Nanopartículas/ultraestructura
4.
Langmuir ; 33(39): 10239-10247, 2017 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-28882034

RESUMEN

Iron oxide nanomaterial is a typical example of a magnetic resonance imaging probe for negative contrast. It has also been shown how this nanomaterial can be synthesized for positive contrast by modification of the composition and size of the core. However, the role of the organic coating in the relaxometric properties is largely unexplored. Here, maghemite nanoparticles with either excellent positive or very good negative contrast performance are obtained by modifying coating thickness while the core is kept unchanged. Different nanoparticles with tailored features as contrast agent according to the coating layer thickness have been obtained in a single-step microwave-driven synthesis by heating at different temperatures. A comprehensive analysis is conducted of how the composition and structure of the coating affects the final magnetic, relaxometric, and imaging performance. These results show how the organic coating plays a fundamental role in the intrinsic relaxometric parameters of iron oxide-based contrast media.

5.
Nanoscale ; 16(13): 6477-6487, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38426659

RESUMEN

Atherosclerosis, a leading cause of cardiovascular diseases requires approaches to enhance disease monitoring and treatment. Nanoparticles offer promising potential in this area by being customisable to target components or molecular processes within plaques, while carrying diagnostic and therapeutic agents. However, the number of biomarkers available to target this disease is limited. This study investigated the use of sphingomyelin-based nanomicelles triggered by sphingomyelinase (SMase) in atherosclerotic plaques. Accumulation of iron oxide-based nanomicelles in the plaque was demonstrated by fluorescence, MR imaging and electron microscopy. These findings demonstrate the possibility of utilising SMase as a mechanism to retain nanoprobes within plaques, thus opening up possibilities for future therapeutic interventions.


Asunto(s)
Aterosclerosis , Nanopartículas , Placa Aterosclerótica , Humanos , Esfingomielina Fosfodiesterasa , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/tratamiento farmacológico , Nanopartículas/uso terapéutico , Imagen por Resonancia Magnética/métodos
6.
Eur J Med Chem ; 237: 114414, 2022 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-35512567

RESUMEN

We have recently described a novel family of compounds of reduced size and dual anti-HIV and anti-EV71 activity that encompasses tripodal and tetrapodal derivatives. The tripodal prototype, AL-470, has a nitro group at the focal point of the central scaffold and three attached tryptophan residues, each of which bearing an isophthaloyl moiety at the C2 position of the indole ring. A nitro to amino substitution has allowed us now to introduce a chemically addressable functionality to perform further structural modifications consisting of both direct and linker-mediated attachment of several aromatic groups, including the fluorescent dye Alexa Fluor 647 and the antibody-recruiting 2,4-dinitrophenyl motif. Some of the derivatives turned out to be more potent and selective than AL-470 against HIV-1, HIV-2 and EV-A71. The fluorescent probe demonstrated a specific tropism for intestines and lungs, two important niches for the human microbiome in health and disease.


Asunto(s)
Dendrímeros , Enterovirus Humano A , Infecciones por Enterovirus , Inhibidores de Fusión de VIH , VIH-1 , Dendrímeros/química , Inhibidores de Fusión de VIH/farmacología , VIH-2 , Humanos , Internalización del Virus
7.
ACS Appl Mater Interfaces ; 13(38): 45279-45290, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34529427

RESUMEN

Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate-functionalized 68Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T1)MRI during the vulnerable stages of the plaque progression.


Asunto(s)
Aterosclerosis/diagnóstico , Medios de Contraste/química , Durapatita/química , Nanopartículas Magnéticas de Óxido de Hierro/química , Calcificación Vascular/diagnóstico por imagen , Alendronato/química , Animales , Aorta/patología , Aterosclerosis/complicaciones , Aterosclerosis/patología , Radioisótopos de Galio/química , Imagen por Resonancia Magnética , Ratones , Imagen Multimodal , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/etiología , Placa Aterosclerótica/patología , Tomografía de Emisión de Positrones , Calcificación Vascular/etiología , Calcificación Vascular/patología
8.
Nanoscale ; 12(45): 22978-22987, 2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33053000

RESUMEN

Radioisotope-labelled nanoparticles permit novel applications in molecular imaging, while recent developments in imaging have enabled direct visualization of biological processes. While this holds true for pathological processes that are stable in time, such as cancer, imaging approaches are limited for phenomena that take place in the range of minutes, such as thrombotic events. Here, we take advantage of bioorthogonal chemistry to demonstrate the concept of nanoparticle-based fast pre-targeted imaging. Using a newly designed nanoparticle that targets platelets we show the applicability of this approach developing thrombo-tag, an in vivo produced nanoparticle that labels thrombi. We show that thrombo-tag allows specific labelling of platelets that accumulate in the injured pulmonary vasculature, or that aggregate in brains of mice suffering thrombotic processes. The fast kinetics and high specificity features of thrombo-tag may critically expand the application of molecular imaging to the most prevalent and debilitating diseases in the clinics.


Asunto(s)
Nanopartículas , Trombosis , Animales , Plaquetas , Ratones , Imagen Molecular , Trombosis/diagnóstico por imagen
9.
ACS Omega ; 4(2): 2719-2727, 2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-31459508

RESUMEN

Synthesizing iron oxide nanoparticles for positive contrast in magnetic resonance imaging is the most promising approach to bring this nanomaterial back to the clinical field. The success of this approach depends on several aspects: the longitudinal relaxivity values, the complexity of the synthetic protocol, and the reproducibility of the synthesis. Here, we show our latest results on this goal. We have studied the effect of Cu doping on the physicochemical, magnetic, and relaxometric properties of iron oxide nanoparticles designed to provide positive contrast in magnetic resonance imaging. We have used a one-step, 10 min synthesis to produce nanoparticles with excellent colloidal stability. We have synthesized three different Cu-doped iron oxide nanoparticles showing modest to very large longitudinal relaxivity values. Finally, we have demonstrated the in vivo use of these kinds of nanoparticles both in angiography and targeted molecular imaging.

10.
J Vis Exp ; (141)2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30531725

RESUMEN

Here, we describe a microwave synthesis to obtain iron oxide nanoparticles core-doped with 68Ga. Microwave technology enables fast and reproducible synthetic procedures. In this case, starting from FeCl3 and citrate trisodium salt, iron oxide nanoparticles coated with citric acid are obtained in 10 min in the microwave. These nanoparticles present a small core size of 4.2 ± 1.1 nm and a hydrodynamic size of 7.5 ± 2.1 nm. Moreover, they have a high longitudinal relaxivity (r1) value of 11.9 mM-1·s-1 and a modest transversal relaxivity value (r2) of 22.9 mM-1·s-1, which results in a low r2/r1 ratio of 1.9. These values enable positive contrast generation in magnetic resonance imaging (MRI) instead of negative contrast, commonly used with iron oxide nanoparticles. In addition, if a 68GaCl3 elution from a 68Ge/68Ga generator is added to the starting materials, a nano-radiotracer doped with 68Ga is obtained. The product is obtained with a high radiolabeling yield (> 90%), regardless of the initial activity used. Furthermore, a single purification step renders the nano-radiomaterial ready to be used in vivo.


Asunto(s)
Compuestos Férricos/síntesis química , Radioisótopos de Galio/química , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Tomografía de Emisión de Positrones/métodos , Medios de Contraste/síntesis química
11.
Contrast Media Mol Imaging ; 2017: 1549580, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29358900

RESUMEN

The combination of the size-dependent properties of nanomaterials with radioisotopes is emerging as a novel tool for molecular imaging. There are numerous examples already showing how the controlled synthesis of nanoparticles and the incorporation of a radioisotope in the nanostructure offer new features beyond the simple addition of different components. Among the different nanomaterials, iron oxide-based nanoparticles are the most used in imaging because of their versatility. In this review, we will study the different radioisotopes for biomedical imaging, how to incorporate them within the nanoparticles, and what applications they can be used for. Our focus is directed towards what is new in this field, what the nanoparticles can offer to the field of nuclear imaging, and the radioisotopes hybridized with nanomaterials for use in molecular imaging.


Asunto(s)
Medios de Contraste , Compuestos Férricos , Imagen Molecular/métodos , Nanopartículas/química , Radioisótopos , Animales , Medios de Contraste/química , Medios de Contraste/uso terapéutico , Compuestos Férricos/química , Compuestos Férricos/uso terapéutico , Humanos , Radioisótopos/química , Radioisótopos/uso terapéutico
12.
Sci Rep ; 7(1): 13242, 2017 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-29038592

RESUMEN

In vivo detection and quantification of inflammation is a major goal in molecular imaging. Furthermore, cell-specific detection of inflammation would be a tremendous advantage in the characterization of many diseases. Here, we show how this goal can be achieved through the synergistic combination of nanotechnology and nuclear imaging. One of the most remarkable features of this hybrid approach is the possibility to tailor the pharmacokinetics of the nanomaterial-incorporated biomolecule and radionuclide. A good example of this approach is the covalent binding of a large amount of a neutrophil-specific, hydrophobic peptide on the surface of 68Ga core-doped nanoparticles. This new nano-radiotracer has been used for non-invasive in vivo detection of acute inflammation with very high in vivo labelling efficiency, i.e. a large percentage of labelled neutrophils. Furthermore, we demonstrate that the tracer is neutrophil-specific and yields images of neutrophil recruitment of unprecedented quality. Finally, the nano-radiotracer was successfully detected in chronic inflammation in atherosclerosis-prone ApoE-/- mice after several weeks on a high-fat diet.


Asunto(s)
Radioisótopos de Galio/metabolismo , Neutrófilos/metabolismo , Neumonía/diagnóstico por imagen , Animales , Modelos Animales de Enfermedad , Radioisótopos de Galio/toxicidad , Células Madre Hematopoyéticas/metabolismo , Ratones , Ratones Endogámicos C57BL , Nanopartículas , Tomografía de Emisión de Positrones , Trazadores Radiactivos
13.
Interface Focus ; 6(6): 20160055, 2016 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-27920894

RESUMEN

Nowadays, thanks to the successful discoveries in the biomedical field achieved in the last two decades, a deeper understanding about the complexity of mechanistic aspects of different pathological processes has been obtained. As a consequence, even the standard therapeutic protocols have undergone a vast redesign. In fact, the awareness about the necessity to progress towards a combined multitherapy in order to potentially increase the final healing chances has become a reality. One of the crucial elements of this novel approach is that large amounts of detailed information are highly needed and in vivo imaging techniques represent one of the most powerful tools to visualize and monitor the pathological state of the patient. To this scope, due to their unique features, nanostructured materials have emerged as attractive elements for the development of multifunctional tools for diagnosis and therapy. Hence, in this review, the most recent and relevant advances achieved by applying multifunctional nanostructures in multimodal theranosis of different diseases will be discussed. In more detail, the preparation and application of single multifunctional nano-radiotracers based on iron oxides and enabling PET/MRI dual imaging will be firstly detailed. After that, especially considering their highly promising clinical potential, the preparation and application of multifunctional liposomes useful for multimodal imaging and therapy will be reviewed. In both cases, a special focus will be set on the application of such a multifunctional nanocarriers in cancer as well as cardiovascular diseases.

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