Fernando Herranz

Spanish National Research Council | CSIC · Instituto de Química Médica

Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of...

Nanoemulsions (NE) are lipid nanocarriers that can efficiently load hydrophobic active compounds, like palmitoyl-L-carnitine (pC), used here as model molecule. The use of design of experiments (DoE) approach is a useful tool to develop NEs with optimized properties, requiring less experiments compared to trial-and-error approach. In this work, NE w...

Nanoemulsions (NE) are lipid nanocarriers that can efficiently load hydrophobic active compounds, like palmitoyl-L-carnitine (pC), used here as model molecule. The use of design of experiments (DoE) approach is a useful tool to develop NE with optimized properties, requiring less experiments compared to trial-and-error approach. The optimized formu...

Background: Alzheimer’s disease (AD) is the most common cause of dementia. It is a multifactorial degenerative disease pathologically characterized by intracellular neurofibrillary tangles and extracellular deposition of amyloid. An early hemostatic dysregulation is also present and contributes to an increment in clot formation, leading to hypoperf...

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...

Abstract Multifunctional magnetic nanocomposites based on mesoporous silica have a wide range of potential applications in catalysis, biomedicine or sensing. Such particles combine responsiveness to external magnetic fields with other functionalities endowed by the agents loaded inside the pores or conjugated to the particle surface. Different appl...

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...

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. He...

Background 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 n...

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in th...

The BlueNative page (BNGE) gel has been the reference technique for studying the electron transport chain organization since it was established 20 years ago. Although the migration of supercomplexes has been demonstrated being real, there are still several concerns about its ability to reveal genuine interactions between respiratory complexes. More...

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 [ ¹⁸ F]FNa is the gold standard, showing a large uptake in the whole skeleton. Here, we push the field towards t...

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 min...

Hypothesis Superparamagnetic MnxFe3-xO4 nanoparticles are promising materials for applications in biomedicine and other fields. Small variations in the Mn/Fe ratio have a strong impact on the properties of the nanoparticles. Those variations may be caused by the synthesis itself and by common post-synthesis manipulations like surface modification....

Advanced uses of smartphones are changing lifestyles, and may have a great impact in materials science in the near future. In this work, the use of these devices to develop fast, simple, and cheap methods to characterize magnetic nanoparticle suspensions is tested. A series of dilutions of a wide library of magnetic nanoparticles, composed of iron...

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...

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 bee...

Background Here we evaluated the feasibility of PET with Gallium-68 (⁶⁸Ga)-labeled DOTA for non-invasive assessment of myocardial blood flow (MBF) and extracellular volume fraction (ECV) in a pig model of myocardial infarction. We also aimed to validate MBF measurements using microspheres as a gold standard in healthy pigs. Methods 8 healthy pigs...

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 di...

New doped inorganic nanocrystals (NC) consisting on iron oxide and other metal integrated into the structure have been synthesized in one-step by adapting the oxidant precipitation synthesis route for magnetite. Different metals have been chosen to confer extra and unique properties to the resulting magnetic heteronanostructure: Co and Gd for enhan...

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 synthesi...

Here, we describe a microwave synthesis to obtain iron oxide nanoparticles core-doped with⁶⁸Ga. 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...

The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduc...

The combination of radioisotopes and nanomaterials is creating a new library of tracers for molecular imaging, exploiting the sensitivity of nuclear imaging techniques and the size-dependent properties of nanomaterials. This new approach is expanding the range of applications, including the possibility of theranostics. Among the many different comb...

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ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosph...

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 comp...

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 mo...

Iron oxide nanomaterial is a typical example of magnetic resonance imaging probe for negative contrast. It has also been shown how this nanomaterial can be synthesised for positive contrast by the modification of the composition and size of the core. However, the role of the organic coating in the relaxometric properties is largely unexplored. Here...

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) are well-known for their anticoagulant properties. There is also currently a growing interest in using LMWH in targeted cancer therapy. In particular, several types inhibit heparanase, a key enzyme overexpressed in the tumor microenvironment that promotes angiogenesis progression...

Iron oxide nanoparticles are one of the most important materials for magnetic resonance imaging. The possibility of multifunctionalization, lack of toxicity, and variety of compositions make them ideal for many applications. Furthermore, the new generation of nanoparticles for “positive” contrast will increase even more their utility, particularly...

Background In vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of 68Ga-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres....

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...

Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 ± 5 nm in diameter) and to vary the aggregation state in order to study their effect on relaxometric and heating properties. Two different coating strategies have been deeply dev...

A fast and reproducible microwave-driven protocol has been developed for the synthesis of neridronate-functionalized nanoparticles. Starting from the synthesis of hydrophobic nanoparticles, our method is based on an adaptation from thermal decomposition method to microwave driven synthesis. The new methodology produces a decrease in the reaction ti...

Combination of complementary imaging techniques, like hybrid PET/MRI, allows protocols to be developed that exploit the best features of both. In order to get the best of these combinations the use of dual probes is highly desirable. On this sense the combination of biocompatible iron oxide nanoparticles and 68Ga isotope is a powerful development f...

Iron oxide nanoparticles have long been studied as a T2 contrast agent in MRI due to their superparamagnetic behavior. T1-based positive contrast, being much more favorable for clinical application due to brighter and more accurate signaling is, however, still limited to gadolinium-or manganese-based imaging tools. Though being the only available c...

The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well-defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanop...

Multifunctional nanoparticles are usually produced by sequential synthesis, with long multi-step protocols. We report here a generic modular strategy for the parallel one-step multifunctionalization of different hydrophobic nanoparticles, by non-covalent interactions between the fatty acid binding sites of the bovine serum albumin and the aliphatic...

We report the synthesis of micellar phosphatidylcholine-coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid-coated Fe3O4 nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obta...

A fast and reproducible microwave-driven process has allowed us to synthesise Neridronate-functionalised nanoparticles. Contrary to traditionally the phosphate groups decorate the outside layer of the particles providing Ca2+ binding properties in vitro and selective accumulation in vivo in the atheroma plaque. In vivo and ex vivo detection by T2-w...

The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the differen...

The combination of nanotechnology, imaging techniques, and biomedicine has produced astonishing results in many fields, and now forms part of clinical practice in areas such as drug delivery, contrast agents, and hyperthermia cancer treatment. In cardiovascular research several new agents have been reported to permit the in vivo imaging, by multipl...

In this study, we have developed an approach for the synthesis of magnetic nanoparticles coated with three different polyethylene glycol-derived molecules (PEG). The influence of the coating on different properties of the nanoparticles has been studied. Magnetite nanoparticles (7 and 12 nm in diameter) were obtained via thermal decomposition of a c...

We present here the synthesis of several new isoalloxazine cyclophanes containing electroactive anthraquinones linked by aliphatic chains of different lengths. Such structural changes provide different interchromophoric orientations leading to the tuning of the rate of the photoinduced electron transfer process from the anthraquinone unit towards t...

We present here the synthesis of several new isoalloxazine cyclophanes containing electroactive anthra-quinones linked by aliphatic chains of different lengths. Such structural changes provide different inter-chromophoric orientations leading to the tuning of the rate of the photoinduced electron transfer process from the anthraquinone unit towards...

Progress in nanotechnology has led to the creation of a new field, namely, nanomedicine. One fundamental goal of nanomedicine is to develop nanoparticles for diagnosis (through imaging techniques) and treatment, usually termed ‘theranostics’ (therapeutics plus diagnostics). These nanoparticles—specifically, magnetic nanoparticles (MNPs)—should idea...

In this study we report the development of a bioconjugate between superparamagnetic iron oxide nanoparticles and Phl p5a (one of the major allergens from grass pollen). The bioconjugate also contains an optical probe (Alexa647) conjugated to the nanoparticle via biotin-streptavidin association. We show that this conjugate has a range of features th...

The functionalization of iron oxide superparamagnetic nanoparticles (NP) is one of the most active research fields due to the necessity of robust and, particularly, reproducible methods for the attachment of new biomolecules on the surface. Olefin metathesis offers many of these features, thanks to the new family of catalysts, especially Hoveyda-Gr...

Here we present an aqueous route for the synthesis of uniform magnetite nanoparticles with sizes around the monodomain diameter (20-100 nm). The method is based on the precipitation of an Fe(II) salt in a mild oxidant in hydroalcoholic solutions, and leads to highly uniform and crystalline magnetic nanoparticles in a single step. Colloidal suspensi...

The combination of nanoparticles, gene therapy, and medical imaging has given rise to a new field known as gene theranostics, in which a nanobioconjugate is used to diagnose and treat the disease. The process generally involves binding between a vector carrying the genetic information and a nanoparticle, which provides the signal for imaging. The s...

A series of bis(dicyclohexylphosphino)methane (dcpm)-containing gold(I) thiolate complexes with urea receptors, 1-3, has been successfully designed and synthesized, and their photophysical and anion-binding properties have been studied. The linker between the thiolate and the urea group, and the electronic environment of the urea moiety, have been...

The synthesis, the Structural characterization and electrochemical and photophysical properties of new linear (OFn) and macrocyclic (MFn) bichromophoric systems containing one flavin and one naphthalene moiety, separated by (CH(2))(n) alkyl chains (n = 4 or 6), are reported, The elect rochernical properties of OF4, OF6, MF4, MF6 were investigated b...

The structure in solution and in the solid state of (+)-biotin methyl ester is discussed based on NMR chemical shifts measured in CDCl(3) Solution and in the solid state together with GIAO calculations at the B3LYP/6-311++G** theoretical level. In the solid state, only the extended conformation exists while in CDCl(3) solution a small amount of a I...

The CD3epsilon subunit of the T cell receptor (TCR) complex undergoes a conformational change upon ligand binding that is thought to be important for the activation of T cells. To study this process, we built a molecular dynamics model of the transmission of the conformational change within the ectodomains of CD3. The model showed that the CD3 dime...

A novel software (VSDMIP) for the virtual screening (VS) of chemical libraries integrated within a MySQL relational database is presented. Two main features make VSDMIP clearly distinguishable from other existing computational tools: (i) its database, which stores not only ligand information but also the results from every step in the VS process, a...

A new methodology for the synthesis of hydrophilic iron oxide nanoparticles has been developed. This new method is based on the direct chemical modification of the nanoparticles' surfactant molecules. Using this methodology both USPIO (ultrasmall super paramagnetic iron oxide) (hydrodynamic size smaller than 50 nm) and SPIO (super paramagnetic iron...

A new method for the rapid synthesis of water-dispersed superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles was investigated. The oxidation of the double bond was carried out by the use of a typical oxidizing reagent such as potassium permanganate. A phase-transfer catalyst, such as benzyltrimethyla...

This review presents an overview of some recent magnetic resonance (MR) techniques for pharmaceutical research. MR is noninvasive, and does not expose subjects to ionizing radiation. Some methods that have been used in pharmaceutical research MR include magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) methods, among them,...

study the binding mode of biotin related compounds with artificial hosts, we have developed a new tool to be used as a guide to test their behaviour prior to their synthesis. In that way, we have considered a set of 23 complexes comprising biotin and urea derivatives with synthetic hosts to develop a Partial Least Squares Cross-Validated (PLS-CV) m...