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A new method simple and efficient for the preparation of Oligonucleotide-protein conjugates

Oligonucleotide-protein conjugates have important applications in biomedicine. Four units of NANBIOSIS have collaborated to come across with more simple and efficient methods for the preparation of these conjugates.

In the publication of the research results, a new method is described in which a bifunctional linker is attached to thiol-oligonucleotide to generate a reactive intermediate that is used to link to the protein. Having similar conjugation efficacy compared with the classical method in which the bifunctional linker is attached first to the protein, this new approach produces significantly more active conjugates with higher batch to batch reproducibility. In a second approach, direct conjugation is proposed using oligonucleotides carrying carboxyl groups. These methodologies have been applied to prepare nanoconjugates of an engineered nanoparticle protein carrying a T22 peptide with affinity for the CXCR4 chemokine receptor and oligomers of the antiproliferative nucleotide 2′-deoxy-5-fluorouridine in a very efficient way. The protocols have potential uses for the functionalization of proteins, amino-containing polymers or amino-lipids in order to produce complex therapeutic nucleic acid delivery systems.

Protein production and DLS have been partially performed by the NANBIOSIS Units of CIBER-BBN  U1 Protein Production Platform (PPP) at IBB-UAB  and  U6 Biomaterial Processing and Nanostructuring Unit of CIBER-BBN and ICMAB-CSIC. Also, NANBIOSIS U18 of Nanotoxicology at the Hospital de la Santa Creu i Sant Pau has been used and the team of researcher counted with the NANBIOSIS expertise of U29 Oligonucleotide Synthesis Platform (OSP) at IQAC-CSIC

Article of reference:

Avino, Anna; Unzueta, Ugutz; Cespedes, Maria Virtudes; Casanova, Isolda; Vazquez, Esther; Villaverde, Antonio; Mangues, Ramon; Eritja, Ramon. Efficient bioactive oligonucleotide-protein conjugation for cell-targeted cancer therapy. CHEMISTRYOPEN 8, 3 (382-387), 2019

https://doi.org/10.1002/open.201900038
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A CXCR4-targeted nanocarrier achieves highly selective tumor uptake in diffuse large B-cell lymphoma mouse models

Researchers of NANBIOSIS Unit 1 and NANBIOSIS Unit 18,  led by Ramón Mangues, have published the article titled CXCR4-targeted nanocarrier achieves highly selective tumor uptake in diffuse large B-cell lymphoma mouse models .

One-third of diffuse large B-cell lymphoma patients are refractory to initial treatment or relapse after rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. In these patients, CXCR4 overexpression (CXCR4+) associates with lower overall and disease-free survival. Nanomedicine pursues active targeting to selectively deliver antitumor agents to cancer cells, a novel approach that promises to revolutionize therapy by dramatically increasing drug concentration in target tumor cells. In the study carried out at NANBIOSIS ICTS the resarchers intravenously administered a liganded protein nanocarrier (T22-GFP-H6) targeting CXCR4+ lymphoma cells in mouse models to assess its selectivity as a nanocarrier, by measuring its tissue biodistribution in cancer and normal cells. No previous protein-based nanocarrier has been described to specifically target lymphoma cells. T22-GFP-H6 achieved a highly selective tumor uptake in a CXCR4+ lymphoma subcutaneous model, as detected by fluorescent emission. We demonstrated that tumor uptake was CXCR4- dependent because pretreatment with AMD3100, a CXCR4 antagonist, significantly reduced tumor uptake. Moreover, in contrast to CXCR4+ subcutaneous models, CXCR4- tumors did not accumulate the nanocarrier. Most importantly, after intravenous injection in a disseminated model, the nanocarrier accumulated and internalized in all clinically relevant organs affected by lymphoma cells, with negligible distribution to unaffected tissues. Finally, the researchers obtained antitumor effect without toxicity in a CXCR4+ lymphoma model by T22-DITOX-H6 administration, a nanoparticle incorporating a toxin with the same structure as the nanocarrier. Hence, the use of T22-GFP-H6 nanocarrier could be a good strategy to load and deliver drugs or toxins to treat specifically CXCR4-mediated refractory or relapsed diffuse large B-cell lymphoma without systemic toxicity.

The bioluminescent follow-up of cancer cells and nanoparticle biodistribution and toxicity studies has been performed in the ICTS NANBIOSIS, using its  unit 18 of Nanotechnology of CIBER-BBN and Hospital Sant Pau The Protein production has been partially performed by the Protein Production Platform (PPP) Unit 1 of ICTS NANBIOSIS of CIBER-BBN and IBB-UAB.

Article of reference:

Aïda Falgàs, Victor Pallarès, Ugutz Unzueta, María Virtudes Céspedes, Irene Arroyo-Solera, María José Moreno, Alberto Gallardo, María Antonia Mangues, Jorge Sierra, Antonio Villaverde, Esther Vázquez, Ramon Mangues, and Isolda Casanova.  A CXCR4-targeted nanocarrier achieves highly selective tumor uptake in diffuse large B-cell lymphoma mouse models. Haematologica 2019

doi:10.3324/haematol.2018.211490

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Inkjet printing and paper sensors to control different analytes with low cost technologies

‘I investigate, I am CSIC’ is a competition hold by The Spanish National Research Council (CSIC) for its doctoral students to disseminate their doctoral thesis. Through short videos of maximum duration of 3 minutes, predoctoral scientists explain their research and results in an informative language.

Miguel Zea, a member of the NANBIOSIS U8 Micro– Nano Technology Unit presents his video explaining how paper sensors can be manufactured to control different analytes with low cost technologies such as Inkjet Printing.

A jury composed of five experts in communication or scientific dissemination will choose eight videos taking into account the originality, impact, convenience and consistency of the video content. In addition, clarity will be valued when exposing the research work and the communicative capacity of the participant. The votes of the public through the YouTube channel of the Postgraduate Department will decide the selection of two other participants.

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NANBIOSIS Unit 18 expands its equipments and capabilities

NANBIOSIS U18 Nanotoxicology Unit, led by Dr. Dr. Ramón Mangues, has recently added new equipment as a result of its participation in the project FICTS1420-20, selected by the MINECO for co-financing by the FEDER Program in ICTS 2014-2020.

The new equipment consists in a Autostainer System for the automation of manual staining methods used in Immunohistochemistry, pharmacodiagnostic, immunofluorescence and chromogenic development for in situ hybridization (AUTOSTAINER-TOX). Includes small equipment for deparaffinization, hydration and antigenic unmasking of paraffin-embedded tissue, complete kit for deparaffinization, hydration and antigenic unmasking of paraffin-embedded tissue. The equipment management software allows monitoring of staining status, request requests, and reporting and obtaining statistics.

European Regional Development Fund
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“Tips and tricks to achieve good results at the bench”

The IBEC Core Facilities team, coordinating NANBIOSIS U7 Nanotechnology Unit has celebrated the 6th edition of the Workshop “Tips and tricks to achieve good results at the bench”.

This workshop is focused on fundamental basic aspects of working in a Chemistry/Biology laboratory: process of performing an experiment, from previous planning until the moment of leaving the bench.

The workshop was divided in two parts:

  • Introduction and overview to the Good Laboratory  Practices.
  • Highly interactive and practical daily lab situations with real equipment.

Upon completion of this workshop participants are able to understand the basics of good laboratory practices, plan an experiment taking into account all the steps necessary to perform it, use several basic equipment (scale, centrifuge, pHmeter, biosafety cabinet/sterile technique, handing liquids) and classify several types of hazardous waste.

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Carlos Rodriguez-Abreu (NANBIOSIS U12) keynote speaker in OKINAWA COLLOIDS 2019


Carlos Rodriguez-Abreu, Scientific Director of NANBIOSIS U12 Nanostructured liquid characterization unit has been invited speaker at OKINAWA COLLOIDS 2019 conference in Okinawa, Japan on November 3 to 8, 2019 in the session Foams / Bubbles / Emulsions and Microemulsions.
Foams and emulsions stabilized by surfactants, amphiphilic polymers and solid particles are essential formulations for developing pharmaceuticals, cosmetics, foods and so on. Recently, many functional systems have been proposed including stimuli responsive materials, biocompatible materials, and environmental affinity materials. The topics of this session include a wide range of subjects: physical properties, phase behaviors and new functions of these systems.

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NANBIOSIS internal dissemination day

NANBIOSIS has celebrated today the second edition of NANBIOSIS internal dissemination day, at the ICMAB-CSIC, Barcelona.

The Day has been focuss on the staff that deals with the day-to-day work of the units, especially technical staff. The event was attended by technicians and coordinators of the units of Catalonia and Aragon (almost 30 face-to-face assistants) and has been followed through the streaming broadcast by the other units.

The day has been presented by the NANBIOSIS Scientific Director Jaume Veciana and the Nerea Argárate Coordinator, followed by a round of presentations by the attendees and their work in the different NANBIOSIS units.

The first part has focused on the Cutting Edge Biomedical Solutions as integral solutions to the problems that arise in biomedical research integrating the expertise of several units presented by Nerea Argarate, as well as several presentations from the units of the Minima invasion Surgery Center Jesus Usón de Cáceres CCMIJU by Javier García, Jorge Bote and Verónica Crisóstomo focused on potential internal collaborations, synergies and complementarities in NANBIOSIS between the CIBER, CCMIJU and Bionand units.

Javier García Casado CCMIJU

The second part dealt with the implementation of quality systems, the NANBIOSIS coordinator has presented the NANBIOSIS Quality Plan and Arnau Jaumandreu (NANBIOSIS Unit 6 Technician) has made a good summary of the steps to follow in the implementation of a quality system with recommendations from its experience in the process followed by unit 6, all followed by a debate.

Arnau Jaumandreu

In the last part Anna May Masnou (Head of Communication and Dissemination of ICMAB-CSIC) has spoken about the use of the NANBIOSIS brand and communication channels, the dissemination of science and its returns. The day has ended with a space for debate.

Anna May Masnou ICMAB-CSIC
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NANBIOSIS in the NEW BOOK of the UNIQUE SCIENTIFIC AND TECHNICAL INFRASTRUCTURES (ICTS)

We are pleased to inform that the new book of Unique Scientific and Technical Infrastructures (ICTS) has been published by the Spanish Ministery of Innovation, Science and Universities with the collaborations of the ICTS.

The Spanish Map of Unique Scientific and Technical Infrastructures (ICTS), goups biomedical technologies, cleanrooms, supercomputers, advanced lasers, telescopes, underground laboratories, synchrotrons, particle accelerators, biological reserves, solar, oceanic and hydraulic platforms, oceanographic research ships, and polar bases in Antarctica. A total of 29 ICTS, made up of 62 nodes, allow for ambitious research projects that attract first-rate talent and enhance the technological and innovative industry capacities.

“Through a one-stop system, NANBIOSIS provides comprehensive solutions that are tailored to the challenges thaat researchers face in biomedicine… its configuration means pioneering multidisciplinary studies can be conducted. Some examples are outlined below.”

NANBIOSIS ICTS

Among these examples, several results combining the expertise of several Units of NANBIOSIS: an original method to prepare smaller nanoparticles of polylactic-co-glycolic acid (PLGA) functionalised with cell-penetrating peptides (CPP), which penetrate the cell membrane and release controlled drug doses into the cells; an innovative medication administration system based on emerging bionanotechnology with protein nanoparticles that selectively deliver lead the therapeutic agent to the tumour cells or a bioactive surgical mesh, covered with adult stem cells, to reduce the inflammatory process associated with implanting this type of material that proved a beneficial effect on the biocompatibility in animal models.

As Pedro Duque, Spanish Minister of Innovation, Science and Universities says in its prelude “The Unique Scientific and Technical Infrastructures described in this book are crucial for Spain and its science, technology, and innovation. I encourage you to browse the pages of this book and discover the state-of-the-art infrastructures that represent the scientific and technological capacity that exists in Spain today. You won’t regret it

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Agreement signed with MINECO for the allocation of FEDER funds for NANBIOSIS ICTS

In the framework of the FEDER Program in ICTS 2014-2020, a project related to the ICTS NANBIOSIS has been selected by the Ministry of Science, Innovation and Universities for co-financing with FEDER funds of the European Regional Development Funds program.

An agreement has been signed between the Ministry of Science, Innovation and Universities and the Institute of Bioingeniería of Catalonia (IBEC) for the implementation of the project “Mask Aligner Team for the unit of Nanotechnology (U7) of Nanbiosis” cofinanced by FEDER Performance Program 2014-2020.  The total budget of the project amounts to € 117.000, with 50% financing with FEDER Funds.

IBEC isprocessing the necessary contracting procedures for the execution of this project.

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I ONLINE Course on Introduction to Quality Management in Laboratories in the Biosanitary Field

The Jesús Usón Minimally Invasive Surgery Center (JUMISC), organizes the 1st ONLINE Course on Introduction to Quality Management in Laboratories in the Biosanitary Field.

The course will count with the expertise Beatriz Moreno Lobato, Scientific Director of NANBIOSIS Unit 19 CLINICAL TEST LAB, among others.

The Course is directed to middle-level technicians: Auxiliary Care of Nursing and Pharmacy and Parapharmacy and also to higher degree technicians: Pathological and Cytodiagnostic Anatomy, Oral Hygiene, Image for Diagnosis and Nuclear Medicine, Clinical and Biomedical Laboratory, Dental Prosthetics, Dietary

The course has a capacity for forty attendees and registration is now open here:

The course program consists of:
Thematic Unit 1: Quality Management Systems (7.5h) (15h student dedication)

  • Historical justification and principles of quality management (1,5h) (J Sánchez)
  • Quality Assurance Systems (J Sánchez)
  • ISO 9001 (1,5h) (J Sánchez)
  • ISO 17025 Standard (1,5h) (J Sánchez)
  • BPL regulations (1,5h) (J Fco Guillén)
  • Quality Philosophy. New strategies (1,5h) (J Sánchez)

Thematic Unit 2: Quality in the field of the laboratory (8.5h) (17h student dedication)

  • Generalities and Management in a Clinical Analysis Laboratory (2h) (B Moreno)
  • Safety standards in laboratories (2h) (J Boat)
  • Quality in other laboratories in the biomedical field (4,5h) (N Hernández / J García / N Picado)

Thematic Unit 3: Analytical Quality (4h) (8h student dedication)

  • Definition of analytical quality. General aspects (B Moreno)
  • Analytical tests (B Moreno)
  • Management and conservation of samples. Analytical Interferences (B Moreno)
  • Validation of analytical methods (B Moreno)
  • Calibration and equipment management. Quality and PNT manuals (J Fco Guillén / B Moreno)

Thematic Unit 4: Introduction to GLP (4h) (8h student dedication)

  • Regulation and relationship with other standards (J Fco Guillén)
  • ISO 13485 and other related standards (J Fco Guillén)
  • Documentation and Quality Assurance (J Fco Guillén)
  • BPL applications (B Moreno)

Final exam and Satisfaction Survey (2h)

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