News U6

Nanoprobes for the next generation of Optical Imaging

Judit Morlà Folch, CIBER-BBN Researcher in Nanomol Group and NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit at ICMAB-CSIC is giving the seminar “Nanoprobes for the next generation of Optical Imaging“, today Monday, 5 October 2020 at 12 pm, Hosted by Nora Ventosa, Nanomol Group in the cycle of Online ICMAB PostDoc Talk.

Online Invited Seminar by Zoom. Register here to attend.

About the Seminar: Molecular imaging plays a vital role in the healthcare sector, since abnormal conditions and diseases are often diagnosed through imaging, while therapeutics methods used for the treatment of the abnormalities are often guided by imaging. Optical imaging is a highly sensitive technique and low-cost procedure in comparison to tomography, Magnetic Resonance Imaging (MRI) or ultrasounds among the other forms of imaging currently employed. Among the imaging agents, fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-established fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability

Judit Morlà Folch began her postdoc in 2008 at New Jersey Institute of Technology (NJIT, EEUU) under the Marie Curie Tecniospring and Postdoctoral Programme in collaboration with ICMAB-CSIC (Nanomol Group), where she is nowadays working on the development of fluorescent organic nanoparticles for bioimaging.

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NANBIOSIS researchers featured in the 15th Edition of Spanish Researchers Ranking

The 15th edition of the Webometrics Ranking of World Universities has been published, ranking researchers in Spain as well as Spaniards doing research abroad. A total of 11 Directors of NANBIOSIS units appear on the most recent list, featured on the top 2000. The list is ordered by the h-index, a metric that calculates research impact based on a correlation of papers published and number of citations, and then by number of citations. The result is a list of whose’s publications have had more impact online.

NANBIOSIS researchers featured are Fernando Albericio (#207), scientific director of U3 Synthesis of Peptides Unit, Ramón Martínez Máñez (#342) U26 NMR: Biomedical Applications II, Jaume Veciana (#459) U6 Biomaterial Processing and Nanostructuring Unit, José Luis Pedraz (#906) U10 Drug Formulation unit, Jesús Santamaría (#912) U9 Synthesis of Nanoparticles Unit, Ramón Eritja (#1022) U29 Oligonucleotide Synthesis Platform (OSP), Pablo Laguna (#1153) U27 High Performance Computing, Antoni Villaverde (#1249) U1 Protein Production Platform (PPP), Laura Lechuga (#1511) U4 Biodeposition and Biodetection Unit M.Pilar Marco (#1517), U2 Custom Antibody Service (CAbS), and Josep Samitier (#1836) U7 Nanotechnology Unit.

This list reflects on the impact online publication can have as a tool to share knowledge.

For further information: here

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Expoquimia hosts the INDUSTRIAL DIALOGUES Webinars with Nora Ventosa

The International Meeting for Chemistry Expoquimia is hosting the INDUSTRIAL DIALOGUES Webinars, a total of 4 seminars discussing different topics related to the cores of the triennial meeting: circular economy, digitalization, and technology transference. This last topic will be covered by Nora Ventosa, Scientific Coordinator of NANBIOIS Unit 6Biomaterial Processing and Nanostructuring Unit

On 4 June, Nora Ventosa, Nora Ventosa will be moderating the round table on the topic of technology transference both as a researcher of the Nanomol group, from CIBER-BBN and ICMAB-CSIC, and as part of the Expoquimia Organizing Comitée. The discussion will be focused on the topic “Creating tools to make innovation a reality. Science and Industry in Action”.

You can register to this webinars on the Expoquimia website and follow Expoquimia on Twitter for more updates on the event!

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New fluorescent organic nanoparticles to see the invisible

A new nanomaterial for bioimaging has been developed by researchers at NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring Unit from the Nanomol group from ICMAB-CSIC and CIBER-BBN . The researchars are also members of the TECNIO technology transfer network ACCIÓ-Generalitat de Catalunya, together with the New Jersey Institute of Technology (NJIT, USA) and the University of Parma (UNIPR, Italy). The results of the study are the result of the TECNIOspring PLUS project co-financed by ACCIÓ and the European Commission.

It is true that it is very difficult to understand what happens in our bodies if we are unable to visualise it. For example, we currently know that tumour cells have the capacity to grow without control thanks to various microscopic techniques that have allowed us to enlarge them to such an extent that we have been able to see each cell perfectly. The design of microscopes and the optical and electronic engineering behind them has advanced very rapidly in recent years. In fact, the 2014 Nobel Prize in Chemistry was awarded to researchers Eric Betzig, William E. Moerner and Stefan Hell, for the development of super-resolution fluorescence microscopy. These advances have made it possible to see even what is inside cells, reaching the nanometer scale with high resolution.

Now, what happens when we are not able to see what we are looking for? This is where fluorescent probes come into play, molecules that provide a signal: they emit light at a certain wavelength once they are excited. These probes must meet a series of requirements, among which are: they must have a high luminosity or brightness, be totally biocompatible, and have high photo-stability and high dispersibility in physiological media.

The Nanomol group has developed new fluorescent probes, specifically fluorescent organic nanoparticles (FONs). These new FONs are based on Quatsomes (QSs), nanovesicules produced by the same group through a green technology (Delos-susp, Nanomol Technologies SL), which are charged with fluorophores or fluorescent molecules – specifically two types of carbocyanins. The nanoparticles have an average diameter of 120 nm and have demonstrated good biocompatibility and high stability, both over time and once exposed to high power laser irradiation.

Characterization of nanovesicles was made at the ICTS “NANBIOSIS”, more specifically by the Unit 6 Biomaterial Processing and Nanostructuring Unit of CIBER-BBN.

“The brightness achieved is especially relevant: these new fluorescent nanoparticles are about 100 times brighter than other commercial fluorescent nanoparticles, such as Quantum Dots, thus allowing the acquisition of high quality images” explains Judit Morla-Folch, postdoctoral researcher of the Nanomol group at the ICMAB and first author of the study, published in the journal ACS Appl. Mater. Interfaces.

In addition, these nanoparticles have another singularity, and that is that they experience Förster resonance energy transfer, usually abbreviated as FRET. This phenomenon allows for improved image acquisition as it significantly reduces self-absorption and therefore background noise during bioimage acquisition. In addition, the FRET effect allows the integrity of the nanoparticle to be monitored, a great advantage for biomedical applications where it is necessary to know when the nanovesicle remains as a whole or it disintegrates.

In summary, the fluorescent organic nanoparticles (FONs) developed by the Nanomol group of the ICMAB-CSIC in collaboration with the NJIT (USA) and the UNIPR (Italy) constitute a promising platform for bioimaging and for the design of medical diagnostic kits.

Cover Figure: The new fluorescent organic nanoparticles allow to improve the visualization of cells and tissues under the microscope.

Reference article:

Dye-Loaded Quatsomes Exhibiting FRET as Nanoprobes for Bioimaging
Judit Morla-Folch, Guillem Vargas-Nadal, Tinghan Zhao, Cristina Sissa, Antonio Ardizzone, Siarhei Kurhuzenkau, Mariana Köber, Mehrun Uddin, Anna Painelli, Jaume Veciana, Kevin D. Belfield, and Nora Ventosa
ACS Appl. Mater. Interfaces 2020, 12, 18, 20253–20262
DOI: 10.1021/acsami.0c03040

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Scientists from NANBIOSIS selected by Barcelona Activa “Preacceleration” Program

Nora Ventosa and Nathaly Segovia, (Scientific Director and Coordinator of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit from CIBER-BBN and ICMAB_CSIC), have been selected as part of the NARTIC Project team for an incubation program by Barcelona Activa. NARTIC is a biotech project for the development of molecular therapy based on Quatsomes for diseases such as cancer.

The NARTIC project has recently been selected for the 6th edition of the Preacceleration Program, an incubation program developed by Barcelona Activa for starting ventures with a high technological impact.

The project team includes two researchers from the Molecular Nanoscience and Organic Materials (NANOMOL) group (from CIBER-BBN and ICMAB-CSIC): Nora Ventosa, as scientific advisor, and Nathaly Segovia, as scientific consultant for technology transfer. The rest of the team is formed by Ariadna Boloix, PhD fellow between the ICMAB and the Vall d’Hebron Research Institute (VHIR), as entrepreneur, Miquel Segura, researcher at VHIR, as scientific advisor, and Martí Archs, Innovation & Tech Transfer Project Manager at VHIR, as innovation and tech transfer consultant.

The project has already developed a laboratory scale proof of concept for their nanomedicine, which uses RNA molecules conjugated to Quatsomes to design a biocompatible lipidic nanoparticle that transports RNA molecules, like microRNAs or siRNAs, and releases them within cancerous cells to induce an anti-tumoral activity. This has been achieved through collaboration between the Recerca Translacional del Càncer Infantil i de l’Adolescència group at the Vall d’Hebron Research Institute (VHIR) and the NANOMOL team at ICMAB.

This program will allow to further define the business model for the project, as well as kickstart their access to the market, through workshops with experts in the field, covering topics like product discovery, lean start ups, and intelectual property, amongst others. They will also get access to the MediaTIC incubator and the possibility of a 5.000€ prize at the end of the process.

For further information: here

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Peptide functionalized nanoliposomes for biomolecule intracellular delivery, prepared using compressed CO2

The PhD Researcher Dolores Bueno researcher of NANOMOL Group and NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring Unit (from CIBER-BBN and ICMAB-SCIC) has defended her PhD thesis today, 20 March 2020, by videoconference from the ICMAB Meeting Room. No public was allowed due to the drastic measures of containment taken to tackle COVID-19.

Peptide functionalized nanoliposomes for biomolecule intracellular delivery, prepared using compressed CO₂

Abstract: Fabry disease is a rare disease caused by a gene mutation on the X-chromosome, which encodes α-galactosidase A (GLA) enzyme. The lack of GLA causes the accumulation of globotriaosylceramide at the lysosomes. The actual treatment is based in the enzyme replacement therapy (ERT), the intravenous administration of the enzyme. Nanotechnology is a powerful tool to develop enzyme-loaded nanosystems in order to ameliorate ERT efficacy.

DELOS-SUSP (Depressurization of an Expanded Organic Solution-Suspension) methodology enables the production of small unilamellar vesicles using compressed CO₂. DELOS-SUSP allows the simultaneous encapsulation of different bioactives like RGD peptide and GLA in liposomes. This Thesis has used liposomes with RGD and GLA to generate a solid proof of concept for the treatment of Fabry disease.

Supervisor:

Nora Ventosa Rull, NANOMOL Group, ICMAB-CSIC Scientific Director of NANBIOSIS Unit 6
Elisabet González Mira, NANOMOL Group, ICMAB-CSIC

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New COVER in Chemistry. A European Journal: an active organic radical stable agains racemization!

The journal Chemistry. A European Journal features in its COVER the recently published article “An enantiopure propeller‐like trityl‐brominated radical: Bringing together a high racemization barrier and an efficient circularly polarized luminescent magnetic emitter” authored by rearserchers of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit, led by Jaume Veciana (CIBER-BBN, ICMAB-CSIC)

Nowadays, it is necessary to know the increasingly specific requirements of electronic devices in order ot be able to find new multifunctional materials that allow obtaining more efficient devices. This article represents a step forward in the field of organic free radicals. Organic free radicals act as polarized light emitters synthesizing and studying the two optically active enantiomers of a new brominated derivative of the trityl radical, which show no evidence of racemization up to 60 ° C for more than two hours, due to the great steric hindrance imposed by the bulky atoms of Br that have as substituents. This fact has allowed to determine its great efficiency of luminescence of polarized light despite its purely organic nature. In addition, this result suggests that new, very improved radicals can be obtained thanks to the wide synthetic possibilities offered by Br atoms.

More information can be found in the Full Paper by I. Ratera, A. G. Campaña, J. Veciana, et al. (DOI: 10.1002/chem.202000098).

See the cover website here (DOI: 10.1002/chem.202000463)

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Rare diseases Day February 29: combating Fabry Disease

29 of February is a ‘rare’ date and February, a month with a ‘rare’ number of days, has become a month to raise awareness about rare diseases and their impact on patients’ lives. Since 2008 thousands of events happen every year all around the world and around the last day of February.

NanoMed Spain Platform and the Hospital of Sant Joan de Déu have organized the NanoRareDiseaseDay to present the latest innovations in the field of Nanomedicine for the treatment and diagnosis of rare diseases (diseases affecting less than 5 people per 10,000 inhabitants). Nora Ventosa, Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit (CIBER-BBN / ICMAB-CSIC) presented Smart4Fabry a European project with the aim of reducing the Fabry disease treatment cost and improve the life-quality of Fabry disease patients

Fabry disease is one of the rare diseases that currently lack a definitive cure. It is cause by lysosomal storage disorders (LSDs): the deficiency of α-Galactosidase A (GLA) enzyme activity result in the cellular accumulation of neutral glycosphingolipids, leading to widespread vasculopathy with particular detriment to the kidneys, heart and central nervous system.

Smart-4-Fabry has been conceived to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration compared to the actual treatment with non-formulated GLA. Four units of NANBIOSIS participate in the project:

– U1 Protein Production Platform (PPP) led by Neus Ferrer and Antony Villaverde at IBB-UAB accomplish the production and purification in different expression systems for R&D purposes.

– U3 Synthesis of Peptides Unit led by Miriam Royo at IQAC-CSIC performs all the chemical process of the Smart-4-Fabry project, i.e. design and synthesis of peptides used as targeting ligands in the nanoliposome formulation

– U6 Biomaterial Processing and Nanostructuring Unit led by Nora Ventosa and Jaume Veciana at ICMAB-CSIC undertakes tasks related to the manufacture of the nanoliposome formulation of GLA enzyme and the physico-chemical characterization (this unit counts with plants at different scales, from mL to L, which allow process development by QbD and process scale-up, as well as instrumental techniques for assessment of particle size distribution, particle concentration, particle morphology and stability, and Z-potential)

– U20 In Vivo Experimental Platform led by Simó Schwartz and Ibane Abásolo at VHIR to carry out the non-GLP preclinical assays of the project (in vivo efficacy, biodistribution and tolerance/toxicity assays).

For further information about Fabry disease and the Smart4Fabry project: here

Nora Ventosa explaining the progress of the smart4fabry
project on nanoliposomes development for the treatment of Fabry disease
(Pictures by Nanomed Spain)

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Fabry disease & Smart4Fabry project

The Fabry disease (FD) is a lysosomal storage disorder (LSD) that currently lacks an effective treatment. Lysosomes are spherical vesicles, which contain hydrolytic enzymes found in nearly all animal cells. LSDs are caused by lysosomal dysfunctions, usually because of the deficiency of a single enzyme required for the metabolism of macromolecules such as lipids, glycoproteins and mucopolysaccharides. Fabry disease is a progressive, X-linked inherited disorder caused by deficiency or absence of the α-galactosidase A (GLA) activity, an enzyme involved in the glycosphingolipid metabolism. The substrates of GLA are glycosphingolipids, being the primary substrate the globotriaosylceramide (Gb3). Therefore, the failure of GLA activity leads to progressive intracellular accumulation of Gb3, in many cells, particularly in renal epithelial cells, endothelial cells, pericytes, vascular smooth muscle cells, cardiomyocytes, and neurons of the autonomic nervous system, leading to multisystemic clinical symptoms. First clinical signs of FD occur during childhood and, over time, microvascular lesions of the affected organs progress leading to early death. It affects mostly men but serious cases have also been reported in women.

There are currently three products authorized in the EU for the treatment of FD. Two products available in EU since 2001 for Enzymatic Replacement Therapy (ERT), Replagal (Shire Human Genetic Therapies AB) and Fabrazyme (Genzyme Europe B.V.), which have to be i.v. administered every other week. The ERT strategy is based on supplying recombinant GLA to cells, reversing several of the metabolic and pathologic abnormalities. There is a third product in the EU market since 2016, which is based on the chaperone migalastat hydrochloride (Galafold Amicus Therapeutics UK Ltd), designed to selectively and reversibly bind with high affinity to the active sites of certain mutant forms of GLA, facilitating proper protein folding and allowing for correct trafficking of the mutant enzyme. However, it is a genotype-specific treatment (only one-third to one-half of mutations may be amenable).

To date, no direct comparisons exist between Fabrazyme and Replagal but significant clinical benefits compared with placebo, however, have been demonstrated with ERT, with positive effects on the heart, kidneys, nervous system and quality of life. Of note, a stabilization of renal function was only observed at an early phase of FD.

ERT success with free GLA is limited mainly due to the instability and low efficacy of the exogenously administered therapeutic enzyme. Furthermore, some patients can develop immune responses after receiving the infused recombinant enzyme. Clinical data has confirmed that the immunological consequences of ERT may impair efficacy in some patients. Furthermore, the short elimination t_1/2of the enzyme and the need for repeated administration of large amounts of enzyme are other limitations of current ERT. In addition, GLA does not cross of the Blood Brain Barrier (BBB), which prevents the product for reducing the Gb3 deposits in the central nervous system (CNS). Moreover, it is a lifelong treatment which becomes a burden for the health system due to its extremely high cost.

Therefore, there is a need for other therapeutic strategies, which can either serve as primary or supplemental treatments. Gene and substrate reduction therapies constitute alternative therapies which are at present under investigation.

The European “Smart-4-Fabry” project aims to develop a new nanoformulation based on the encapsulation of the GLA enzyme in nanoliposomes, to improve the current ERT of FD. A Consortium formed by ten partners, including private companies and public institutions in Europe and Israel, has been granted (July 2017) with a Horizon2020 financial programme by the European Commission (H2020-NMBP-2016-2017; call for nanotechnologies, advanced materials, biotechnology and production; Proposal number: 720942-2).

The project is expecting to last for 48 months and contemplates the necessary activities to advance a nanoliposome formulation of GLA enzyme, i.e., nano-GLA, from an experimental proof of concept up to an advanced nonclinical stage of development. The S4F should complete an advanced regulatory safety and toxicology package supporting future nano-GLA clinical development in patients with FD.

To the best of S4F knowledge, there is no previous experience on the encapsulation of a GLA for treating FD patients following an ERT approach.

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#RareDiseaseDay: Fabry lysosomal disease

Rare Disease Day is annually held on the last day of February in more than 100 countries with the main objective of raising awareness about rare diseases and their impact on the life of patients to the general public and in particular to policy makers, public authorities, industry representatives, researchers and professionals. Rare diseases are those that affect less than 1 in 2000 people. There are more than 300 million people living with one or more than more than 6000 rare diseases worldwide identified.

Among the events organized we wont to mention the Nano Rare Diseases Day held in Barcelona on February 27, organized by the Hospital de Sant Joan de Déu and the NanoMed Spain Platform, where the latest innovations in the field of Nanomedicine for the treatment and diagnosis of these diseases will be announced, with themes ranging from early diagnosis, controlled release of drugs or the development of new therapies. During this day, experts in Nanomedicine from different fields – research, business, clinical practice, health authorities, patients, etc. – will present the latest advances and give us the opportunity to discover the progress generator that Nanomedicine means for health as creator of new opportunities in the diagnosis and treatment of minority diseases.

Nora Ventosa, Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit (CIBERBBN-ICMAB_CSIC) will explain the European Smart-4-Fabry Project: use of nanotechnology for the development of a new drug for the treatment of Fabry lysosomal disease where four units of NANBIOSIS colaborate.

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