Search

Iron oxide nanoparticles (IONP) have been hailed as potential game-changers in biomedical imaging owing to their biocompatibility and size-dependent properties. One area where IONP has shown particular promise is magnetic resonance imaging (MRI), which traditionally uses superparamagnetic nanomaterials to produce negative contrast that darkens the tissues where nanoparticles accumulates. Unfortunately, this hypointense signal is a major drawback for clinical applications because it can make it difficult to identify the accumulated probes. As a result, researchers are exploring alternative options that can incorporate the advantages of IONP while also possessing valuable properties for molecular imaging. To achieve this goal, the most effective method involves not only utilizing positive contrast in MRI applications but also combining IONP with the unparalleled sensitivity of nuclear imaging techniques, for example, using radioisotopes to create PET/(T)MRI multimodal probes. To create such probes, various factors must be considered, including the radiolabeling strategy employed and overall complexity of the final nanoprobe. These nanoradiomaterials offer novel possibilities that span beyond the molecular imaging field, showing potential for the development of radiopharmaceuticals and theranostics.

CRUE-CSIC (Acuerdos Transformativos 2021), The coating composition of nanomedicines is one of the main features in determining the medicines' fate, clearance, and immunoresponse in the body. To highlight the coatings' impact in pulmonary administration, two micellar superparamagnetic iron oxide nanoparticles (SPION) were compared. These nanoparticles are similar in size and charge but have different coatings: either phosphatidylcholine (PC-SPION) or bovine serum albumin (BSA-SPION). The aim of the study was to increase the understanding of the nano-bio interaction with the cellular and non-cellular components of the lung and underline valuable coatings either for local lung-targeted drug delivery in theranostic application or patient-friendly route systemic administration. PC-SPION and BSA-SPION were deposited in the alveoli by in vivo instillation and, despite the complexity of imaging the lung, SPION were macroscopically visualized by MRI. Impressively, PC-SPION were retained within the lungs for at least a week, while BSA-SPION were cleared more rapidly. The different lung residence times were confirmed by histological analysis and supported by a flow cytometry analysis of the SPION interactions with different myeloid cell populations. To further comprehend the way in which these nanoformulations interact with lung components at the molecular level, we used fluorescence spectroscopy, turbidity measurements, and dynamic light scattering to evaluate the interactions of the two SPION with surfactant protein A (SP-A), a key protein in setting up the nanoparticle behavior in the alveolar fluid. We found that SP-A induced aggregation of PC-SPION, but not BSA-SPION, which likely caused PC-SPION retention in the lung without inducing inflammation. In conclusion, the two SPION show different outcomes from interaction with SP-A leading to distinctive fate in the lung. PC-SPION hold great promise as imaging and theranostic agents when prolonged pulmonary drug delivery is required., Ministerio de Ciencia e Innovación (MICINN), Gobierno Vasco.ELKARTEK Program, BBVA Foundation, Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, TRUE, pub

Non-invasive imaging methodologies, especially nuclear imaging techniques, have undergone an extraordinary development over the last years. Interest in the development of innovative tracers has prompted the emergence of new nanomaterials with a focus on nuclear imaging and therapeutical applications. Among others, organic nanoparticles are of the highest interest due to their translational potential related to their biocompatibility and biodegradability. Our group has developed a promising new type of biocompatible nanomaterials, sphingomyelin nanoemulsions (SNs). The aim of this study is to explore the potential of SNs for nuclear imaging applications.

Sandra Díez-Villares,1– 3 Juan Pellico,4,5 Noemí Gómez-Lado,6 Santiago Grijalvo,7,8 Sandra Alijas,1 Ramon Eritja,7,8 Fernando Herranz,5,9 Pablo Aguiar,6 María de la Fuente1,2 1Nano-Oncology and Translational Therapeutics group, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, Santiago de Compostela, 15706, Spain; 2Biomedical Research Networking Center on Oncology (CIBERONC), Madrid, 28029, Spain; 3University of Santiago de Compostela (USC), Santiago de Compostela, 15782, Spain; 4School of Biomedical Engineering & Imaging Sciences, King’s College London, St. Thomas’ Hospital, London, SE1 7EH, UK; 5Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, 28029, Spain; 6Nuclear Medicine Department and Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, Santiago de Compostela, 15706, Spain; 7Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, E-08034, Spain; 8Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain; 9NanoMedMol Group, Instituto de Química Medica (IQM),Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28006, SpainCorrespondence: María de la FuenteNano-Oncology Unit and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital (CHUS), Building C, Floor − 2, Lab 18, Travesía da Choupana s/n, Santiago de Compostela, ES15706, SpainTel +34 981 955 704Email maria.de.la.fuente.freire@sergas.esBackground and Purpose: Non-invasive imaging methodologies, especially nuclear imaging techniques, have undergone an extraordinary development over the last years. Interest in the development of innovative tracers has prompted the emergence of new nanomaterials with a focus on nuclear imaging and therapeutical applications. Among others, organic nanoparticles are

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.

Iron oxide nanoparticles have been extensively utilised as negative (T2) contrast agents in magnetic resonance imaging. In the past few years, researchers have also exploited their application as positive (T1) contrast agents to overcome the limitation of traditional Gd3+ contrast agents. To provide T1 contrast, these particles must present certain physicochemical properties with control over the size, morphology and surface of the particles. In this review, we summarise the reported T1 iron oxide nanoparticles and critically revise their properties, synthetic protocols and application, not only in MRI but also in multimodal imaging. In addition, we briefly summarise the most important nanoparticulate Gd and Mn agents to evaluate whether T1 iron oxide nanoparticles can reach Gd/Mn contrast capabilities., Ministerio de Economía y Competitividad (MINECO), Ministerio de Ciencia e Innovación (MICINN), Unidad de Excelencia Maria de Maeztu, Gobierno Vasco, Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

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.

Iron oxide nanoparticles have been extensively utilised as negative (T2) contrast agents in magnetic resonance imaging. In the past few years, researchers have also exploited their application as positive (T1) contrast agents to overcome the limitation of traditional Gd3+ contrast agents. To provide T1 contrast, these particles must present certain physicochemical properties with control over the size, morphology and surface of the particles. In this review, we summarise the reported T1 iron oxide nanoparticles and critically revise their properties, synthetic protocols and application, not only in MRI but also in multimodal imaging. In addition, we briefly summarise the most important nanoparticulate Gd and Mn agents to evaluate whether T1 iron oxide nanoparticles can reach Gd/Mn contrast capabilities

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. ©

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 / T-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 Ga iron oxide nano-radiomaterials provide simultaneous PET and T-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.

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.