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“The almighty graphene”, a podcast by Elisabet Prats

Elisabet Prats Alfonso, a researcher in the team coordinating NANBIOSIS U8 Micro– Nano Technology Unit explains in a podcast her most recent research based on the functionalization of chemical and biochemical sensor platforms as well as the characterization of materials such as graphene for both neuronal recording and biomarker detection. Her work is part of the Graphene Flagship project in which she collaborates with relevant European groups.

Eli Prat as a researcher Ph.D. in Chemistry and also dedicated to dissemination is a great exemple for the NANBIOSIS aim to encourage STEAM scientific vocations especially among girls.

In addition, she is the author, together with Helena González and Oriol Marimón, of the book “Elementum and the great robbery of Nurú” (La Esfera de los Libros, 2020), a scientific novel aimed at children .

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Nora Ventosa appointed Research Professor under the Materials Science

Nora Ventosa, the Scientific Director of NANBIOSIS U6 of Biomaterial Processing and Nanostructuring Unit (and IP of the NANOMOL Group of CIBERBBN at ICMAB-CSIC) has been appointed Research Professor in the last call of the Spanish National Reserach Council (CSIC)

This elective process for the selection and appointment of career civil servant, by internal promotion, in the Scale of Research Professors of Public Research Organisms had oppen 6 new positions for Professors under the Materials Science.

Nora Ventosa is a Chemical Engineer by the Institut Químic de Sarrià (IQS) and Doctor in Chemistry by the Universitat Ramon Llull. Her research is focused on green chemistry, soft materials and nanobiochemistry. She is devoted to develop and apply new methodologies, based on compressed fluids, in order to gain control of molecular self-assembly in solution.

Prof. Ventosa is also co-founder of the spin-off Nanomol Technologies, vicepresident of the Societat Catalana de Química (SCQ-IEC), member of the Administration Council of ACCIÓ, the Catalan Government agency for the promotion of the competitiveness within companies, and President of the TECNIO Research Association. She has participated, organized and directed more than 50 research projects, funded by different national and international agencies, public, private and industrial, including the European projects Smart4Fabry (Smart multifunctional GLA-nanoformulation for Fabry disease) or Phoenix (Open Innovation Test Bed for Enabling Pharmaceutical Innovative Products).

U6: Biomaterials processing and Nanostructuring unit

 Unit 6 of NANBIOSIS, on Biomaterials processing and Nanostructuring unit from CIBER-BBN, hosted at ICMAB-CSIC, with Scientific Director Nora Ventosa, from the Nanomol-Bio research group. The U6 gathers several laboratories, perfectly equipped, to perform the mission of this facility: the development, characterization, and large-scale production of molecular biomaterials of therapeutic or biomedical interest, with controlled micro-, nano- and supramolecular structure. One example of Key-Enabling-Technology (KET) available in this unit in collaboration with the SME Nanomol Technologies (spin off of CSIC) is a simple and green one-step methodology, DELOS, based on the use of compressed fluids (CF), such as CO2, to prepare particulate materials with precise and reproducible structural characteristics at micro-, nano- and supramolecular levels (size, shape, internal structural gradients, supra­molecular organization and crystalline purity). This example shows one of the singularities of this unit is that counts with CF–based plants at different scales, from mL to L, which allow process development by QbD and process scale-up. Recently U6 NANBIOSIS, together with the Soft Scientific and Technical Service, was accredited with the ISO9001 certification for the standard quality control system. 

Congratulations Nora!

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Antitumoral nanoparticles with multiple activities, a close reality.

Conventional chemotherapeutics used to fight cancer promote off-target damage in cells and organs that are not affected by the disease. This major drawback may be overcome with the development of tumor-targeted therapies, in which the antitumoral drugs are selectively delivered to tumoral cells using the efficient recognition between a receptor overexpressed in these cells and its ligand, without promoting off-side effects in the rest of the body.

The group of Nanobiotechnology (NBT) from the Institut de Biotecnologia i Biomedicina (IBB-UAB), led by Prof. Antonio Villaverde, develops a new concept of pharmaceuticals based on protein nanoparticles, in close collaboration with the group of Oncogenesis and Antitumor Drugs (GOA) from the Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau) and the group of Nucleic Acids Chemistry from the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), respectively lead by Prof. Ramon Mangues and Prof. Ramon Eritja. This research is conducted in the frame of the Director plan of CIBER-BBN, an excellence center from the Instituto de Salud Carlos III, to which all the groups belong, being assisted by three Nanbiosis ICTS units (U1, Protein Production Platform; U18, Nanotoxicology Unit; U29, Oligonucleotide Synthesis Platform).

The generated pharmaceuticals are selective for metastatic stem cells, responsible of cancer propagation, recurrence and bad prognosis, that overexpress in their surface the CXCR4 receptor, present in 23 distinct human neoplasias. Using a precise protein engineering, we generate multi-functional protein nanoparticles that remain in the bloodstream for long times and selectively enter and destroy metastatic stem cells, thus contributing to stop cancer progression. In the last years, we have employed two main strategies in the development of antitumoral protein nanoparticles. On one side, current chemotherapeutics already used in clinics in non-targeted approaches, such as Floxuridine or Monomethyl Auristatin E, are chemically linked to targeted protein nanoparticles that serve as drug delivery systems and comprise an inert scaffold, a polyhistidine tag and a targeting peptide that directs their effect to the CXCR4-tumor. On the other side, the inert scaffold of our protein nanoparticles is replaced by toxins, venoms or other death-inducer proteins that confer the protein nanoparticle an intrinsic antitumoral activity, without the need of delivering chemical drugs. Both strategies are protected by intellectual property rights.

Recently, we have explored the possibility of combining both strategies to generate intrinsically toxic nanoparticles loaded with conventional chemotherapeutics in a single pharmacological entity. This way, we seek to potentiate their antitumoral effect and face the appearance of resistances in the tumor. In this initial step, the concept proposed has been demonstrated as fully feasible, as stable nanoparticles that contain both the toxin and the loaded chemotherapeutics were generated. Although these novel nanomaterials do not improve toxic antitumoral activities in CXCR4+ tumor cell lines, this research has been crucial to identify the main bottleneck of the technology, that is achieving a precise control of the drug-binding site in order to maintain the antitumoral activity of targeted toxins, which must act at the same time as active principle and as anchoring site for chemical drugs.

This novel platform recruits in a single pharmacological entity different therapeutic actions and may open a broad investigation field in the design of antitumoral drugs. The current results of this project have been published in the scientific journal Acta Biomaterialia and presented in the international conference NALS2022 by Eric Voltà-Durán.

By Eric Voltà-Durán

Reference article – Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles  https://doi.org/10.1016/j.actbio.2020.11.018

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Improving quality of MR spectra from mouse brain. MRSI-detected pattern in glioblastoma patients

Work performed at Unit 25 of Nanbiosis ICTS of “NMR: Biomedical ApplicationsI” is being shown at the Joint annual meeting ISMRM-ESMRMB (May 7-12th) London, with the participation of CIBER-BBN group members Ana Paula Candiota, Silvia Lope-Piedrafita, Miquel Cabañas (abstract 1), Carles Arús, Gulnur Ungan, Margarida Julià-Sapé, Alfredo Vellido and Carles Majós (abstract 2).

In the first abstract, entitled “High resolution Multi-voxel spectroscopy using CSI-semi-LASER for mouse brain preclinical studies” we focused into improving quality of MR spectra obtained from mouse brain, a key factor when trying to pursue metabolomic-based biomarkers.

The second abstract, entitled “MRSI-detected pattern in glioblastoma patients one month after concomitant chemoradiotherapy” presented a study with a retrospective MRSI set of 31 glioblastoma patients and investigation of spectral patterns predictive of true progression or pseudoprogression.

The International Society for Magnetic Resonance in Medicine (ISMRM) and The European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) are prestigious scientific societies devoted to magnetic resonance-based studies at international and European levels with participation of the most renowned scientifics in the field. This year, the international and european events are joined into a single event (https://www.ismrm.org/22m/)

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Induced pluripotent stem cells in disease modelling and experimental therapies: cardiovascular perspective

On the 20th of May, we will be receiving an international visit at the  Unversity of Zaragoza from Pr. Józef Dulak from Jagiellonian University, Kraków, Poland. The title of the talk will be “Induced pluripotent stem cells in disease modelling and experimental therapies: cardiovascular perspective“.

The invited lecture is programed within the framework of the European CISTEM project, in wich the University of Zaragoza participates through CIBER-BBN group TME lab – NANBIOSIS U13 Tissue & Scaffold Characterization Unit.

The event will take place at 12:00 in the I3A SEMINAR (2nd floor) of Campus Rio Ebro, of University of Zaragoza

Induced pluripotent stem cells (iPSC) are generated by genetic reprogramming of somatic cells and thanks to the ability to differentiate into almost all cells types of the organism they offer the enormous possibilities for investigating disease mechanisms, drug sensitivity and safety and for experimental regenerative approaches.  iPSC thus became the indispensable tools of current medial biotechnology and received additional input thanks to the development of the CRISPR/Cas9 gene editing.

In this lecture PR. Józef Dulak will review his research in which iPSC and CRISPR/Cas9 gene editing is applyed for investigating the iPSC-differentiation to cardiomyocytes, endothelial cells and other cell types linked with the disease affecting vascular system, heart and the skeletal muscles. The special attention will be on discussing the potential of iPSC for diabetes and Duchenne muscular dystrophy disease modelling.

Application of iPSC-derived cardiomyocytes offer the chance for effective cell therapy of heart failure and this will be addressed in regard to recently published studies.

  1. Sci Rep. 2015 Feb 26;5:8597. doi: 10.1038/srep08597.
  2. Stepniewski J, et al., Dulak J. Heme oxygenase-1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells. IUBMB Life. 2018 Feb;70(2):129-142. doi: 10.1002/iub.1711. 2018 Jan 9.
  3. Kachamakova-Trojanowska N, Stepniewski J, Dulak J.  Human iPSCs-derived endothelial cells with mutation in HNF1A as a model of maturity-onset diabetes of the young. Cells. 2019 Nov 14;8(11). pii: E1440. doi: 10.3390/cells8111440.
  4. Stępniewski J, et al. Dulak J.  Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, in Contrast to Adipose Tissue-Derived Stromal Cells, Efficiently Improve Heart Function in Murine Model of Myocardial Infarction. Biomedicines. 2020 Dec 7;8(12):578. doi: 10.3390/biomedicines8120578.
  5. Jeż M, et al. Dulak J.  Role of Heme-Oxygenase-1 in Biology of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells. Cells. 2021 Mar 1;10(3):522. doi: 10.3390/cells10030522.
  6. Andrysiak K, Stępniewski J, Dulak J. Human-induced pluripotent stem cell-derived cardiomyocytes, 3D cardiac structures, and heart-on-a-chip as tools for drug research. Pflugers Arch. 2021 Jul;473(7):1061-1085. doi: 10.1007/s00424-021-02536-z. Epub 2021 Feb 24.
  7. Martyniak A, et al, Dulak J. Generation of microRNA-378a-deficient hiPSC as a novel tool to study its role in human cardiomyocytes. J Mol Cell Cardiol. 2021 Jul 28;160:128-141. doi: 10.1016/j.yjmcc.2021.07.007.  
  8. Kachamkova-Trojanowska N, Skoczek D, Dulak J,  Maturity Onset Diabetes of the Young – new approaches for disease modelling. Int J Mol Sci. 2021 Jul 14;22(14):7553. doi: 10.3390/ijms22147553.
  9. Andrysiak K, et al., Dulak J. Generation of DMBi002-A human induced pluripotent stem cell line from patient with Spinal muscular atrophy type 3. Stem Cell Res. 2021 Oct 13;57:102563. doi: 10.1016/j.scr.2021.102563. 
  10. Jelinkova S, Martyniak A, Dulak J, Stępniewski J.   Derivation of human pluripotent stem cell line via CRISPR/Cas9 mediated deletion of exon 3 LAMA2 gene (DMBi001-A-1) Stem Cell Res. 2021 Sep 2;56:102529. doi: 10.1016/j.scr.2021.102529
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OPEN SUBMISSION FOR JOURNAL SPECIAL ISSUE ON OLIGONUCLEOTIDE BASED THERAPIES

Dr. Ramon Eritja, Scientific Director of NANBIOSIS unit 29 of Oligonucleotide Synthesis Platform (OSP) and Dr. Santiago Grijalvo researcher at NANBIOSIS unit 12 of Nanostructured liquid characterization, from CIBER-BBN and IQAC-CSIC, together with Dr. Andreia F. Jorge, from Coimbra Chemistry Centre (CQC), acting as guest editors of journal Pharmaceutics, of MDPI Publisher, welcome authors to submit their articles on special issues on Recent Trends in Oligonucleotide Based Therapies.

In the past few decades, significant efforts have been made towards the clinical application of oligonucleotides. However, the potential of the therapeutic applications of RNA-based strategies have recently been spotlighted after the first approval of mRNA vaccines in response to COVID-19 pandemic. These molecules have the power to tackle targets that are usually considered to be “undruggable” by blocking the translation or transcription of a specific gene by stimulating the degradation of a particular messenger RNA.

This Special Issue aims to collect reviews, original research articles, and short communications covering innovative strategies in the design, synthesis, and characterization of therapeutic oligonucleotides as well as advances in their delivery based on nanotechnologies. Research concerning the study of sequence-specific protein–DNA/RNA interactions will be also considered.

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form.

For all the informations and instructions about the Special Issue, please visit this MDPI page

Deadline for submissions: 31 December 2022

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Wide representation of NANBIOSIS research in NALS 2022 and best Oral Presentation to Eloi Parladé

During the last 27-29 April, the 3rd International Conference on Nanomaterials Applied to Life Sciences 2022 (NALS 2022) has taken place in the Excellence Campus of Universidad de Cantabria in Santander (Spain), organized by the University of Cantabria and Institute Valdecilla-IDIVAL.

NALS 2022 has been a multidisciplinary conference series sharing new results and ideas in the fields of biosensors, lab on a chip, drug delivery nanopharmacy. nanobiotechnology, intelligent nanomaterials, magnetic materials, nanotoxicity, antimicrobials, novel applications of 3d bioprinting and nanoimaging.

NANBIOSIS has been represented at this edition by members of several of its units, among them we must highlight the set of four oral communication presented by members of the Nanobiotechnology group-Unit 1 of NANBIOSIS “Protein Production Platform (PPP)”, from CIBER-BBN and IIB-UAB the talks were delivered by:

Eloi Parladé: “Development of ion-dependent microscale secretory granules for nanomedical applications”

Carlos Martínez-Torró: “Design of a human GFP-like protein scaffold for targeted nanomedicines”

Eric Voltá Durán: “Antitumoral nanoparticles with multiple activities, a close reality”

Jan Atienza-Garriga: “Characterization of protein-only NPs containing amps and analysis of their protection with liposomes and micelles”

They summarized a wide area of the team activities on the design of protein-based protein materials for clinical uses, produced by means of diverse types of cell factories. In particular, antimicrobial peptides, cytotoxic proteins with antitumoral targeting and drug-carrying scaffold proteins are engineered to confer self-assembling properties as either microparticles or nanoparticles, that can be further functionalized with chemical drugs through covalent binding. Microparticles are of special interest as they can be used as slow drug delivery systems for nanostructured drugs upon subcutaneous administration. Alternatively, nanoparticles can be also presented as embedded in liposomes or other micellar structures that stabilize them for enhanced performance.

Three NANBIOSIS units supported the presented research, which has been executed in a highly cooperative way: namely U1 (Protein Production Platform), led by Tony Villaverde U18 (Nanotoxicology), led by Ramón Mangues and U29 (Oligonucleotide Synthesis Platform), led by Ramón Eritja.

Among all the excellent contributions by the team, it is worthy to stress that the prize for the best Oral Presentation was granted to Dr Eloi Parladé.

Other talk by researchers from NANBIOSIS were “Antioxidant-loaded polymeric NPs prepared by nano-emulsion templating for the management of neurological diseases” by Santiago Grijalvo, from NANBIOSIS U12 and  “Exploiting GSH oxidation with nanocatalysts to promote cancer cell death” by Javier Bonet-Aletá from NANBIOSIS U9

On the other hand, Jesús Santamaría,  Scientific Director of NANBIOSIS U9 was a Keynote Speaker in the Conference with the talk: “A change of paradigm in cancer therapy? Using catalysts to make drugs inside the tumor, rather than trying systemic chemotherapy”

NALS 2022 has been an excellent conference, with presentations covering a wide range of topics in nanomaterials for health, and a great opportunity for our researchers, especially for young’s, to let know their collaborative work, as well as make new connections on common research interests, thanks to the good socializing opportunities afforded by the scheduling of the organization conference.

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