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News U3

News U3

Peptide‐Capped Mesoporous Nanoparticles: Toward a more Efficient Internalization of Alendronate.

Osteoporosis is an illness which appears when the osteoblast/osteoclast activities are unbalanced taking place bone resorption (caused by osteoclasts) in higher extension than bone formation (induced by osteoblasts). Alendronate is one of the most used drugs for osteoporosis treatment despite its scarce bioavailability. In an attempt to improve it, gated mesoporous silica nanoparticles, for the controlled release of alendronate, have been synthesized and characterized. These hybrid nanoparticles include labelled alendronate inside the porous, those porous are capped with a peptide designed to be selectively cleaved by cathepsin K enzyme (overexpressed in osteoclasts).

Two CIBER-BBN units of the ICTS NANBIOSIS were implied in the research: the peptide was prepared by U3 Synthesis of Peptides Unit and substances were characterized at U26 NMR: Biomedical Applications II Unit at University of Valencia.

The nanoparticles were internalized by RAW 264.7 macrophages (which could differentiate in osteoclasts) and were able to release its entrapped cargo in the presence of cathepsin K added in the macrophage lysates. From the set with aminopropyl functionalized silica, loaded with nitrobenzofurazan labelled alendronate and capped with the same peptide, 4.2% of the total alendronate amount in contact with the cells is liberated inside them and could produce its therapeutic effect.

Article of reference:

Elena Añón, Ana M. Costero, Pedro Amorós, Jamal El Haskouri, Ramón Martínez‐Mánez, Margarita Parra, Salvador Gil, Pablo Gaviña, M. Carmen Terencio, María Alfonso. Peptide-Capped. Mesoporous Nanoparticles: Toward a more Efficient Internalization of  Alendronate. Chemistry Europe, March 2020

https://doi.org/10.1002/slct.202000417

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A new strategy to synthesize Chol-PEG “on demand”

Researchers of NANBIOSIS U3 Synthesis of Peptides Unit of CIBER-BBN at IQAC-CSIC, led by Miriam Royo, have published an article in the scientific journal ACS Omega that develops a method for the production of cholesterol conjugates to peptide ligands through polyethylene glycol (ND-PEG) not dispersed through a non-hydrolyzable bond.

The developed methodology allows to generate stable, highly pure and well defined Chol-PEG compounds, linked to different lengths of PEG from 4 to 20 units of ethylene oxide through an ether bond. These Chol-PEG compounds were conjugated with different peptides, such as cyclic peptide (RGDfK), gluturation and a Tf1R peptide ligand, preserving the oligomeric purity of the precursors, as demonstrated by analysis by HRMS and NMR. This method allows the systematic synthesis of stable, high-purity Chol-PEGs, bypassing the use of activation groups at each elongation step and thus reducing the number of synthesis steps.

The use of Chol-PEG conjugates has increased in recent years as a component of nanoformulations for applications such as drug administration or imaging systems, due to the ability of Chol to insert into artificial and cell membranes. This ability facilitates the stability of nanovesicles, such as liposomes or others, and entry into cells.

The synthesis of the peptides used in this work was carried out in Unit 3 of NANBIOSIS – ICTS Peptide Synthesis Unit and was developed within the framework of the HORIZON 2020 Smart4Fabry project.

Article of referrence:

Synthesis of Stable Cholesteryl–Polyethylene Glycol–Peptide Conjugates with Non-Disperse Polyethylene Glycol Lengths. Edgar Cristóbal-Lecina, Daniel Pulido, Pau Martin-Malpartida, Maria J. Macias, Fernando Albericio, and Miriam Royo. ACS Omega 2020 5 (10), 5508-5519 https://doi.org/10.1021/acsomega.0c00130

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NANBIOSIS U2, U3 & U29 participate in the POC4CoV project to develop diagnostic technologies for SARS-COV-2

The Spanish Higher Council for Scientific Research (CSIC) will finance the project Point-of-care tests for the rapid detection of SARS-CoV-2 (POC4CoV), whose objective is to have effective diagnostic technologies for Covid-19. The Institute of Microelectronics of Barcelona (IMB-CNM-CSIC), the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and the Institute of Materials Science of Aragon (ICMA) participate in it.

The POC4CoV project aims to develop Point-of-Care (POC) devices for the in vitro diagnosis of SARS-COV-2 infection quickly and reliably, thanks to the use of multiplexed systems and the use of particular biomolecular probes. To do this, POC technological platforms will be used in combination with specific capture biomolecules and nanobiotechnological probes (enzyme bioconjugates and biofunctional plasmonic and magnetic nanoparticles), which will allow the simultaneous detection of different biomarkers (viral RNA and antigens, IgM and IgG) related to Covid-19 disease. The biomolecular complexes will be collected at specific points on the devices where the electrochemical or optical signals will be recorded.

The developed POC platforms will undergo analytical and clinical validation in a clinical setting.

Three units of NANBIOSIS (form CIBER-BBN and IQAC-CSIC) will will take an active participation in the project.

NANBIOSIS Unit 2 Custom Antibody Service (CAbS), will produce antibodies against the Spike protein and other virus proteins, trying to maximize the recognition of those epitopes that differentiate SARS-CoV-2 from other Coronaviruses

NANBIOSIS Unit 3 Synthesis of Peptides Unit will synthesize peptidic sequences that will allow to identify towards which epitopes the immune response is directed, which will allow to develop more specific diagnostic methods.

NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) has designed probes with oligonucleotide sequences that will allow the capture of viral RNA through the formation of high affinity triplex complexes

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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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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in our units, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer in the Scientific Direction of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Laura Lechuga and M.Carmen Estevez in the Direction and Scientific Coordination of U4 Biodeposition and Biodetection Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Mª Virtudes Céspedes in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 
Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS

Thanks to all of you and your teams!

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Antimicrobial peptides are a promising kind of molecules to fight multi-drug resistant bacteria

The project titled “Breaking the boundaries of resistance to antimicrobials; searching for new antimicrobials against multiresistant bacteria: work on polycytonic peptides and lipid nanoparticles (BARNAPA)” in which participates Fernando Albericio, Scientific Director of NANBIOSIS unit 3 Synthesis of Peptides Unit, has been selected by La Marató TV3 and finnaced with 383.276,25 €.

According to Fernando Albericio, the project arises from the need of effective and safer antibiotics to fight resistant and multi-drug resistant bacteria. In this sens, the proyect developed in collaboration with Miquel Vinyas of the UB and with the Stefania Stefani group of the Universita de Catania  looks at antimicrobial peptides as a promising kind of molecules to achieve this goal.

Fernando explains the experimental session of the project: “The synthesis of molecules in the chemical laboratory may yield new cationic peptides analogs optimizing selectivity (increasing activity, reducing toxicity) to develop them as candidates for preclinical development. Natural molecules, such as teixobactin and colistin, may serve as scaffold for unlimited new antimicrobial peptides. Mechanisms of action and spectrum of activity should be elucidated first by means of biophysical studies (electron microscopy, flow cytometry, model membranes, electrophysiology). In addition, preparation of lipid nanoparticles will be carried out to explore new pharmaceutical formulations maintaining antimicrobial activity and reducing unwanted side effects. Testing studied molecules in front of clinical multidrug resistant isolates and biofilms produced by these bacteria will be also accomplished. The eventual synergism between the peptides and conventional antimicrobials has to be explored since previous results are promising. We hopefully expect this project to yield a few candidates and propose new delivery
formulations to start exploratory in vitro and in vivo tests (which should include acute toxicity determination, pharmacokinetics, and development of a model of respiratory infection in mice) to finally transfer it to a pharmaceutical company for further clinical assay and use”.

 

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Two units of NANBIOSIS in the project selected by La Marató TV3 to fight against bacterial infections

La Marató TV3 in its call for biomedical projects in infectious diseases has selected the project “Uses of molecular analysis of Quorum Sensing with the diagnosis of bacterial infections” of the Nb4D group, led by Mª Pilar Marco, Scientific Director of unit 2 of NANBIOSIS and in which Miriam Royo also participates Scientific Coordinator of unit 3 of NANBIOSIS, both in the IQAC-CSIC of Barcelona

The project of the Nanobiotechnology for Diagnosis (Nb4D) group of the CSIC and the CIBER-BBN has been selected among more than 200 candidates as a project of scientific excellence to be funded in the call for biomedical projects of the Fundació la Marató de TV3 and Catalonia Radio. The project, led in the Nb4D group by Dr. M.-Pilar Marco, Scientific Director of unit 2 of NANBIOSIS and Dr. Lluïsa Vilaplana, will be carried out in collaboration with Dr. M.-Teresa Martín (Hospital Vall d’Hebrón) and aims to study the potential of various molecules of Quorum Sensing as diagnostic tools for bacterial infections. The project, financed with € 227,684.84, also has the collaboration of Dr. Miriam Royo, Scientific Coordinator of Unit 3 of NANBIOSIS, of the Multivalent Systems for Nanomedicine group, also belonging to the CSIC and the CIBER-BBN.

The funds raised in the 2017 edition of the Marató de TV3 and Cataluña Radio will finance 36 biomedical research projects of excellence in infectious diseases to promote the creation of new tools for prevention and diagnosis, as well as more efficient treatments with the aim of earning more and more quality of life for patients.

Link to the news:
http://www.ccma.cat/324/la-marato-impulsa-36-projectes-de-recerca-biomedica-en-malalties-infeccioses/noticia/2884103/

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Lysosomal Rare Disorders: Focus on Fabry Disease

Last November 19, Vall d’Hebron held a seminar  on Lysosomal Rare Disorders: Focus on Fabry Disease as  part of the Rare Diseases Program at the Vall d’Hebron Campus, in collaboration with the European Commission, the Center for Biomedical Research Network on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and the CIBBIM-Nanomedicine at Vall d Hebron Research Institute (VHIR) through the Smart-4-Fabry projec

In the  second plenary session, moderated by Nora Ventosa and Simó Schwartz, Scientific Directors of NANBIOSIS units 6 and 20 and devoted to New therapeutic strategies for lysosomal disorders, the speakers presented their findings regarding biomarkers, genetic variants and treatment protocols. Ibane Abasolo, Scientific Coordinator of NANBIOSIS Unit 20 gave a talk on Nanomedicine in lysosomal disorders. Project Smart4Fabry .

The Smart4Fabry project, coordinated by CIBER-BBN and with the participation of NANBIOSIS units U3 Synthesis of Peptides Unit, U6 Biomaterial Processing and Nanostructuring Unit and U20 Functional Validation & Preclinical Research (FVPR), was described in the course of this specific day on lysosomal diseases and Fabry’s disease.

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Peptides, targeting units and drug conjugates

Miriam Royo, Scientific Coordinator of Unit 3 of NANBIOSIS explains in this video the expertise of the unit in the preparation of difficult peptides (Cyclid and polycyclic peptides, stapled peptides and dificult peptides, depsipetides, natural products and libraries, peptidomimetic libraries, peptides as antigens or adjuvants, tarjeted drug conjugates, etc… as well as therapeutic agen-PEG-targeting unit conjugates

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Stimuli-Responsive Functionalization Strategies to Spatially and Temporally Control Surface Properties: Michael vs Diels–Alder Type Additions

NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring and Unit 3 Synthesis of Peptides collaborate in a research whose results are published by The Journal of Physical Chemistry B

Stimuli-Responsive Functionalization Strategies to Spatially and Temporally Control Surface Properties: Michael vs Diels–Alder Type Additions

Adriana R. KyvikCarlos Luque-CorrederaDaniel PulidoMiriam RoyoJaume VecianaJudith Guasch, and Imma Ratera
The Journal of Physical Chemistry B 2018 122 (16), 4481-4490

DOI: 10.1021/acs.jpcb.8b01652

Stimuli-responsive self-assembled monolayers (SAMs) are used to confer switchable physical, chemical, or biological properties to surfaces through the application of external stimuli. To obtain spatially and temporally tunable surfaces, we present microcontact printed SAMs of a hydroquinone molecule that are used as a dynamic interface to immobilize different functional molecules either via Diels–Alder or Michael thiol addition reactions upon the application of a low potential. In spite of the use of such reactions and the potential applicability of the resulting surfaces in different fields ranging from sensing to biomedicine through data storage or cleanup, a direct comparison of the two functionalization strategies on a surface has not yet been performed. Although the Michael thiol addition requires molecules that are commercial or easy to synthesize in comparison with the cyclopentadiene derivatives needed for the Diels–Alder reaction, the latter reaction produces more homogeneous coverages under similar experimental conditions.

 

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