Alvaro Somoza

Madrid Institute for Advanced Studies in Nanoscience (IMDEA Nanociencia), Madrid, Spain · Nanomedicine

Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the releas...

The present study explores the application of X-ray scattering, using synchrotron radiation, to assess the diffusive transport of nanomedicines in tumor on a chip devices fabricated by 3D stereolithography using a resin with high optical and X-ray transmittance. Unlike conventional methods that require fluorescent labeling of nanoparticles, potenti...

1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are becoming increasingly popular building blocks in medicinal chemistry since they are saturated bioisosteres of orthosubstituted phenyl rings. Here we have developed the first enantioselective catalytic strategy based on a Lewis acid-catalyzed [2+2]...

Immunotherapy has emerged as a promising strategy to eradicate cancer cells. Particularly, the development of cancer vaccines to induce a potent and sustained antigen-specific T cell response has become a center of attention. Herein, we describe a novel immunotherapy based on magnetic nanoparticles (MNP) covalently modified with the OVA254-267 anti...

In this work, we describe the synthesis of magnetic nanoparticles composed of a maghemite core (MNP) and three different coatings (dextran, D-MNP; carboxymethyldextran, CMD-MNP; and dimercaptosuccinic acid, DMSA-MNP). Their interactions with red blood cells, plasma proteins, and macrophages were also assessed. CMD-MNP was selected for its good bios...

Natural killer (NK) cells recognise and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted EVs led to the identification of a specific repertoir...

The clinical implementation of magnetic hyperthermia has experienced little progress since the first clinical trial was completed in 2005. Some of the hurdles to overcome are the reliable production of magnetic nanoparticles with controlled properties and the control of the temperature at the target tissue in vivo. Here, forty samples of iron oxide...

At the time of writing, there were 486 761 597 global cases of COVID‐19 with 6 142 735 confirmed deaths (World Health Organization, 4 April 2022). According to the scarcity of information about estimation of cases with mild or no symptoms, it is suggested that they could represent 25–80% of all infections. The majority of these cases remain unteste...

The development of DNA-sensing platforms based on new synthetized Methylene Blue functionalized carbon nanodots combined with different shape gold nanostructures (AuNs), as a new pathway to develop a selective and sensitive methodology for SARS-CoV-2 detection is presented. A mixture of gold nanoparticles and gold nanotriangles have been synthetize...

In this work we present a powerful, affordable, and portable biosensor to develop Point of care (POC) SARS-CoV-2 virus detection. It is constructed from a fast, low cost, portable and electronically automatized potentiostat that controls the potential applied to a disposable screen-printed electrochemical platform and the current response. The pote...

This research raises the potential use of coordination polymers as new useful materials in two essential research fields, allowing the obtaining of a new multiartificial enzyme with the capacity to inhibit the growth of bacteria resistance. The fine selection of the ligands allows the design of a new 2D coordination polymer (CP), with the formula [...

Gold nanotriangles (AuNTs) functionalized with dithiolated oligonucleotides have been employed to develop an amplification-free electrochemical biosensor for SARS-CoV-2 in patient samples. Gold nanotriangles, prepared through a seed-mediated growth method and exhaustively characterized by different techniques, serve as an improved electrochemical p...

We present a fast, reliable and easy to scale-up colorimetric sensor based on gold nanoparticles (AuNPs) to detect the sequences coding for the RdRp, E, and S proteins of SARS-CoV-2. The optimization of the system (so-called “the sensor”) includes the evaluation of different sizes of nanoparticles, sequences of oligonucleotides and buffers, which i...

The COVID-19 pandemic has brought to light the need for fast and sensitive detection methods to prevent the spread of pathogens. The scientific community is making a great effort to design new molecular detection methods suitable for fast point-of-care applications. In this regard, a variety of approaches have been developed or optimized, including...

Gold nanoparticles (AuNPs) can be used as carriers for biomolecules or drugs in cell culture and animal models. Particularly, AuNPs ease their internalization into the cell and prevent their degradation. In addition, engineered AuNPs can be employed as sensors of a variety of biomarkers, where the electronic and optical properties of the AuNPs are...

Stimuli-responsive nanomaterials are very attractive for biomedical applications. They can be activated through external stimuli or by the physico-chemical conditions present in cells or tissues. Here, we describe the preparation of hybrid iron oxide-manganese oxide core-satellite shell nanostructures that change their contrast mode in magnetic res...

Natural killer (NK) cells recognise and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated NK cells and their secreted EVs led to the identification of a specific repertoire of N...

Small molecule drugs, including most chemotherapies, are rapidly degraded and/or eliminated from the body, which is why high doses of these drugs are necessary, potentially producing toxic effects. Several types of nanoparticles loaded with anti-cancer drugs have been designed to overcome the disadvantages of conventional therapies. Modified nanopa...

Mutant p53 proteins result from missense mutations in the TP53 gene, the most mutated in human cancer, and have been described to contribute to cancer initiation and progression. Therapeutic strategies for targeting mutant p53 proteins in cancer cells are limited and have proved unsuitable for clinical application due to problems related to drug de...

Magnetic nanoparticles (MNP) are employed as nanocarriers and in magnetic hyperthermia (MH) for the treatment of cancers. Herein, a smart drug delivery system composed of MNP functionalized with the cytotoxic drug gemcitabine (MNP-GEM) has been thoroughly evaluated. The linker employed is based on a disulfide bond and allows the controlled release...

Uveal melanoma (UM) is an intraocular cancer tumor with high metastatic risk. It is considered a rare disease, but 90% of affected patients die within 15 years. Non-coding elements (ncRNAs) such as long non-coding RNAs (lncRNAs) have a crucial role in cellular homeostasis maintenance, taking part in many critical cellular pathways. Their deregulati...

Cancer is one of the major health problems worldwide, and hence, suitable therapies with enhanced efficacy and reduced side effects are desired. Gene therapy, involving plasmids, small interfering RNAs, and antisense oligonucleotides have been showing promising potential in cancer therapy. In recent years, the preparation of various carriers for nu...

Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. The most widely used method for the preparation of albumin nanoparticles is by desolvation process using glutaraldehyde (GLU) as a cross-linker. Howeve...

Uveal melanoma (UM) is an intraocular tumor which is almost lethal at the metastatic stage due to the lack of effective treatments. In this regard, we have developed an albumin-based nanostructure (ABN) containing AZD8055 (ABN-AZD), which is a potent mTOR kinase inhibitor, for its efficient delivery to the tumors. The drug has been conjugated to AB...

Pancreatic cancer is a usually fatal disease that needs innovative therapeutic approaches since the current treatments are poorly effective. In this study, based on cell lines, triazole-based coordination trimers made with soluble Fe(II) in an aqueous media were explored for the first time as adjuvant agents for the treatment of this condition. The...

Autophagy is an evolutionary conserved physiological process with a fundamental role during development, differentiation, and survival of eukaryotic cells. On the other hand, autophagy dysregulation is observed in many pathological conditions, including cancer. In particular, tumor growth and progression are accompanied and promoted by increased au...

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....

Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effectiv...

There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functio...

In this work, we describe the use of Boron Dipyrromethene (BODIPY) as electron‐withdrawing group for activation of double bonds in asymmetric copper‐catalyzed [3+2] cycloaddition reactions with azomethine ylides. The reactions take place under smooth conditions and with high enantiomeric excess for a large number of different substituents, pointing...

We describe the preparation of two monomers that bear complementary nucleobases at the edges (guanine-2'-deoxycytidine and 2-aminoadenine-2'-deoxyuridine) and that are conveniently protected and activated for solid-phase automated DNA synthesis. We report the optimized synthetic routes leading to the four nucleobase derivatives involved, their cros...

Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of cell invasion and metastasis in cancers. Besides the acquisition of migratory/invasive abilities, the EMT process is tightly connected with the generation of cancer stem cells (CSCs), thus contributing to chemoresistance. However, although EMT represents a relevant therapeuti...

Controlled delivery of multiple chemotherapeutics can improve the effectiveness of treatments and reduce side effects and relapses. Here in, we used albumin-stabilized gold nanoclusters modified with doxorubicin and SN38 (AuNCs-DS) as combined therapy for cancer. The chemotherapeutics are conjugated to the nanostructures using linkers that release...

Despite the extensive genetic and phenotypic variations present in the different tumors, they frequently share common metabolic alterations, such as autophagy. Autophagy is a self-degradative process in response to stresses by which damaged macromolecules and organelles are targeted by autophagic vesicles to lysosomes and then eliminated. It is kno...

In this paper we show that conjugation of magnetic nanoparticles (MNPs) with Gemcitabine and/or NucAnt (N6L) fostered their internalization into pancreatic tumor cells and that the coupling procedure did not alter the cytotoxic potential of the drugs. By treating tumor cells (BxPC3 and PANC-1) with the conjugated MNPs and magnetic hyperthermia (43...

MicroRNAs (miRNAs) are small regulatory RNAs, the dysregulation of which has been associated with the progression of several human diseases, including cancer. Interestingly, these molecules can be used as biomarkers for early disease diagnosis and can be found in a variety of body fluids and tissue samples. However, their specific properties and ve...

Molecular shuttles are the basis of some of the most advanced synthetic molecular machines. In these devices a macrocycle threaded onto a linear component shuttles between different portions of the thread in response to external stimuli. Here, we use optical tweezers to measure the mechanics and dynamics of individual molecular shuttles in aqueous...

Here, we exploit the high force (0.1 pN), spatial (1 nm) and temporal (1 kHz) resolutions of optical tweezers    to quantify and control mechanically the real-time kinetics of individual synthetic molecular shuttles operating at near-physiological conditions, for several hundreds of switching cycles, near equilibriu...

Doxorubicin (DOX) is a frequently used chemotherapeutic drug for breast cancer, but its site specificity and local internalization into tumor cells is rather low. In this paper we conjugated magnetic nanoparticles (MNPs) with DOX and/or a pseudopeptide NucAnt (N6L) as modality to enhance DOX-induced antitumor effects in breast cancer cells (BT474)....

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and around half of the patients develop metastasis and die shortly after because of the lack of effective therapies for metastatic UM. Consequently, new therapeutic approaches to this disease are welcome. In this regard, microRNAs have been shown to have a key role...

An imine-based covalent organic framework (COF) decorated in its cavities with uracil groups has shown selective recognition towards adenine in water. These results show how the confinement of the base-pair inside the COF's pores allows a remarkable selective recognition in aqueous media.

A set of Ru(II) metallopeptides containing the dppz ligand has been synthesized using solid-phase peptide synthesis methods. Fluorescence titration studies show that those metallopeptides featuring an octaarginine tail display a large binding preference for DNA G-quadruplex structures over those lacking the oligocationic domain, and also that the i...

Decades after the birth of supramolecular chemistry, there are many techniques to measure noncovalent interactions, such as hydrogen bonding, under equilibrium conditions. As ensembles of molecules rapidly lose coherence, we cannot extrapolate bulk data to single-molecule events under non-equilibrium conditions, more relevant to the dynamics of bio...

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disea...

Silver nanoclusters (AgNCs) stabilized by oligonucleotides are fluorescent structures, whose properties are attracting researchers from various areas. The two main characteristics that have prompted the development of projects involving AgNCs are: their ease of preparation and their tunable fluorescent properties, which can be modulated simply by t...

We present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides like miRNAs among others. The sensor is based on NaYF4:Yb,Er@SiO2 nanoparticles functionalized with ssDNA that contain azide groups on the 3' ends. In the presence of a target sequence, inter-strand li...

Uveal melanoma is a rare disease accounting for 5% of all melanomas. It is the most common primary intraocular malignant tumor in adults resulting in liver metastasis in 85% of the cases, half of which end up in death. This overwhelming scene has raised up a considerable interest in the development of novel approaches for the treatment of such dise...

The direct reaction between copper nitrate, thymine-1-acetic acid, and 4,4′-bipyridine in water leads to the formation of a blue colloid comprising uniform crystalline nanoribbons (length >1 μm; width ca. 150–185 nm; diameter ca. 15–60 nm) of a coordination polymer. The polymer displays a thymine-based structure freely available for supramolecular...

The direct reaction between copper nitrate, thymine-1-acetic acid, and 4,4′-bipyridine in water leads to the formation of a blue colloid comprising uniform crystalline nanoribbons (length >1 μm; width ca. 150–185 nm; diameter ca. 15–60 nm) of a coordination polymer. The polymer displays a thymine-based structure freely available for supramolecular...

Silver nanoclusters (AgNCs) stabilized by DNA are promising materials with tunable fluorescent properties, which have been employed in a plethora of sensing systems. In this report, we explore their antimicrobial properties in gram positive and gram negative bacteria. After testing 9 oligonucleotides with different sequence and length, we found tha...

Old tricks, new dog: CRISPR/Cas9 is a powerful tool for gene editing that requires an endonuclease (Cas9) and RNA strands. It has been shown that chemical modification of the RNA structures, an approach that has been used to improve the efficiency of RNA interference, can also be applied to enhance the activity of CRISPR/Cas9 and reduce its off-tar...

Gelernte Lektionen: CRISPR/Cas9 ist eine leistungsfähige Methode des Genom-Editing, die eine Endonuklease (Cas9) und RNA-Stränge erfordert. Nun wurde gezeigt, dass chemische Modifikationen der RNA-Strukturen, wie sie in der RNA-Interferenz zur Effizienzverbesserung etabliert sind, ebenfalls genutzt werden können, um die Aktivität des CRISPR/Cas9-Sy...

Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel th...

Au- and iron-based magnetic nanoparticles (NPs) are promising NPs for biomedical applications due to their unique properties. The combination of a gold coating over a magnetic core puts together the benefits from adding the magnetic properties to the robust chemistry provided by the thiol functionalization of gold. Here, the use of Au-coated magnet...

Proteins have been used as templates to stabilize fluorescent metal nanoclusters thus obtaining stable fluorescent structures, and their fluorescent properties being modulated by the type of protein employed. Designed consensus tetratricopeptide repeat (CTPR) proteins are suited candidates as templates for the stabilization of metal nanoclusters du...

In an ever-growing number of investigations it has been shown that nucleic acid templated reactions are useful tools in nucleic acid diagnosis and reaction/drug discovery. Furthermore, applications in materials chemistry are being explored, wherein nucleic acid templates instruct the size-controlled formation of macromolecular materials. Nucleic ac...

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Early treatment may improve any chances of preventing metastatic disease, but diagnosis of small UM is challenging. Up to 95 % of all UMs carry somatic mutations in the G-coupled proteins GNAQ and GNA11 promoting anchorage-independent growth and proliferati...

The delivery of drugs can be improved with the use of different carriers, such as those based on nanoparticles. The nanostructures loaded with the therapeutic molecules should be able to reach the target cells and, what is more, release the drugs efficiently. Ideally, the drugs should be delivered only in the target cells, and not along their way t...