News

Josep Samitier, Scientific Director of NANBIOSIS Unit 7, Panelist in a round table about the current situation of biomedical research

Last month NANBIOSIS Unit 7 Nanotechnology Unit Scientific Director Josep Samitier was one of the panelists in a round table organised by the Cercle de Salut, an association devoted to improving the health system so that it may respond adequately to the challenges posed by society.

In the discussion at the Parc de Recerca Biomèdica de Barcelona (PRBB) entitled ‘L’excel·lència en la recerca, reptes immediats’, Josep and the other participants – ISGlobal director Antoni Plasencia and IrsiCaixa director Bonaventura Clotet – discussed the current situation of biomedical research in Catalonia. In particular, the hot topic under discussion was the impact that recent regulatory and administrative changes may have on its competitiveness.

Samitier is a key figure of influence in this area, not only as president of ACER (the Associació Catalana d’Entitats de Recerca, but also with IBEC being a member of SOMMa, the alliance of the country’s 41 Severo Ochoa and María de Maeztu units. One of SOMMa’s first actions was the document ‘Informe SOMMa: Acciones necesarias para salvaguardar la competitividad de la ciencia’ to attract the attention of politicians to address some of the problems currently hampering research in the country, such as VAT deduction, public contracting, and the hiring of personnel.

The proceedings began with a presentation of the document on behalf of SOMMa by Bruna Vives, managing director of the CRG, and the round table moderator was Jordi Camí, director general of the PRBB and the Fundació Pasqual Maragall. The session was closed by Cercle de Salut vicepresident Lluis Bohigas.

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Judith Guasch, (NANBIOSIS Unit 6) has been granted with a Ramon y Cajal grant from the Spanish Goverment

Judith Guasch holds a senior postdoctoral research position at the NANOMOL group CIBER-BBN at ICMAB-CSIC that coordinates NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring Unit, after being awarded with a TecnioSpring fellowship (Marie Curie Fellow, Cofund – Catalan Government and EU). Since 2017 she is also head of a Max Planck Partner Group (Dynamic Biomimetics for Cancer Immunotherapy) in collaboration with the Max Planck Institute for Medical Research (Heidelberg, Germany). Judith’s research interests are focused on the design, synthesis, and fabrication of multifunctional molecular and supramolecular materials for biomedical applications. Special interest is devoted to study the cell-material interaction for improving novel adoptive cell therapies for the treatment of cancer. She studied Chemistry at the UB (2006) and she received her PhD in 2011 from ICMAB. Afterwards, she carried out postdoctoral research at the Max Planck Institute for Intelligent Systems (Stuttgart, Germany).

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«The combination of nanotechnology with bioengineering and biomedicine allows us to act on the human body on a molecular scale»

Josep Samitier, Scientific Director of NANBIOSIS Unit 7 Nanotechnology Unit, has been highlighted in ‘Dominical’ supplement of the Diari de Girona last week.

More information here

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Parasympathetic tone activity evaluation to discriminate ketorolac and ketorolac/tramadol analgesia level in swine

Francisco M. Sánchez-Margallo, Assistant Director of NANBIOSIS and Scientific Director of JUMISC is co-author of the article “Parasympathetic tone activity evaluation to discriminate ketorolac and ketorolac/tramadol analgesia level in swine”, publish by Anesth Analg. 2018 Jun 14. doi: 10.1213/ANE.0000000000003573. [Epub ahead of print]

Abstract

BACKGROUND:

Evaluation of nociceptive–antinociceptive balance during general anesthesia is still challenging and routinely based on clinical criteria. Analgesic drug delivered may be optimized with parasympathetic tone activity (PTA) monitor. This study compares ketorolac and ketorolac/tramadol balance analgesia using a PTA monitor.

METHODS:

Pain intensity response was assessed using a 0–100 numerical state scale (PTA) after nociceptive stimuli in pigs under stable sevoflurane anesthesia. Bispectral index, heart rate, noninvasive blood pressure, and respiratory parameters were also measured. Animals were divided into 3 groups: without analgesia, ketorolac, and ketorolac/tramadol. Mean values or mean areas under the curve (AUC) in selected time periods were compared over time and between groups through a mixed-model repeated measures analysis of variance and nonparametric Kruskal-Wallis tests, followed by Bonferroni or Dunn’s multiple comparisons.

RESULTS:

It was observed a significant decrease in the PTA AUC mean value after application of the stimulus in animals treated without analgesia and only with ketorolac. The PTA AUC mean value in the control group was significantly lower than the corresponding mean in ketorolac group. The ketorolac/tramadol group showed the highest PTA AUC mean values, significantly different from those obtained for the other 2 groups, with no significant differences detected over time. Bispectral index means showed no statistically significant differences either over time periods or between different treatment groups. Heart rate showed only a statistically significant increase in AUC mean between without analgesia and ketorolac/tramadol group, in the time period after the stimulus application. Noninvasive blood pressure means showed no statistically significant differences over time and between treatment groups.

CONCLUSIONS:

This study shows that a low dose combination of ketorolac and tramadol is sufficient to block the pain responses induced with a needle holder in pigs 20 minutes after its administration. The PTA monitor was able to clearly recognize the analgesic level between treatments and may be used to optimize analgesic drug delivered

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Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin

Researchers of NANBIOSIS Unit 1 and NANBIOSIS Unit 18, led by Prof Antoni Villaverde have published the article “Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin” at SMALL journal.

Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, CXCR4‐targeted nanoparticles. The soluble version of the construct self‐organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4⁺ cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor‐dependent mechanism of cytotoxicity. The insoluble version of T22‐mRTA‐H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22‐mRTA‐H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22‐mRTA‐H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self‐mediated intracellular drug delivery.

See article: https://doi.org/10.1002/smll.201800665

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Prof. Laura Lehuga, new Associate Editor at Analyst Editorial Board

Laura Lechuga, Scientific Director of NANBIOSIS Unit 4 Biodeposition and Biodetection Unit, at Catalan Institute of Nanoscience and Nanotechnology, has joined the Analyst Editorial Board as an Associate Editor from today.

Analyst publishes analytical and bioanalytical research that reports premier fundamental discoveries and inventions and the applications of those discoveries, unconfined by traditional discipline barriers

Laura Lechuga is the CSIC Research Professor at the Catalan Institute of Nanoscience and Nanotechnology, Spain. She is the leader of the CIBER-BBN-ICN2 Nanobiosensors and Bioanalytical Applications Group, which focusses on the technological development of nanophotonic biosensors, their integration into portable lab-on-a-chip platforms and their application in clinical and environmental diagnostics. Professor Lechuga gained her PhD in chemistry in 1992 from the Universidad Complutense de Madrid. Between 2012 and 2015 she was an adjunct professor at the University of Norway within their department of Physics and Technology at the Artic. She has also been a distinguished visiting professor at the School of Electrical and Computer Sciences of the Universidade Estadual de Campinas (Brazil) since 2013.

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Self-assembling toxin-based nanoparticles as self-delivered antitumoral drugs

Scientists of NANBIOSIS Units U1. Protein Production Platform (PPP), and U18. Nanotoxicology Unit, have recently published an article titlled “Self-assembling toxin-based nanoparticles as self-delivered antitumoral drugs” in the Journal of Controlled Release.

Loading capacity and drug leakage from vehicles during circulation in blood is a major concern when developing nanoparticle-based cell-targeted cytotoxics. To circumvent this potential issue it would be convenient the engineering of drugs as self-delivered nanoscale entities, devoid of any heterologous carriers. In this context, we have here engineered potent protein toxins, namely segments of the diphtheria toxin and the Pseudomonas aeruginosa exotoxin as self-assembling, self-delivered therapeutic materials targeted to CXCR4⁺ cancer stem cells. The systemic administration of both nanostructured drugs in a colorectal cancer xenograft mouse model promotes efficient and specific local destruction of target tumor tissues and a significant reduction of the tumor volume. This observation strongly supports the concept of intrinsically functional protein nanoparticles, which having a dual role as drug and carrier, are designed to be administered without the assistance of heterologous vehicles.

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Graphene 2018 with the participation of NANBIOSIS Unit 8

Eli Prats and Eduard Masvidal researchers of NANBIOSIS Unit 8 Micro and Nanotechnology Unit have shown their last results in ECoG recordings and biosensing using graphene based devices at the 8th edition of Graphene Conference series, the largest European Event in Graphene and 2D Materials, which is taken place in Dresden (Germany) from the 26th until the 29th of June 2018.

Eli Prats has spoken on Label-free Direct Detection of Thrombin through graphene SGFET with chemically modified aptamers and Eduard Masvidal has given a talk on Graphene transistors for ultra-slow frequency (< 0.1Hz) in vivo neural recordings showing graphene SGFETs as a promising technology for recording ultra-slow frequencies with high-spatial resolution

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Release of targeted protein nanoparticles from functional bacterial amyloids: A death star-like approach

Sustained release of drug delivery systems (DDS) has the capacity to increase cancer treatment efficiency in terms of drug dosage reduction and subsequent decrease of deleterious side effects. In this regard, many biomaterials are being investigated but none offers morphometric and functional plasticity and versatility comparable to protein-based nanoparticles (pNPs). Researchers of NANBIOSIS units 1 and 18 are co-authors of an article publish by Journal of Controlled Release in which it is described a new DDS by which pNPs are fabricated as bacterial inclusion bodies (IB), that can be easily isolated, subcutaneously injected and used as reservoirs for the sustained release of targeted pNPs. Our approach combines the high performance of pNP, regarding specific cell targeting and biodistribution with the IB supramolecular organization, stability and cost effectiveness. This renders a platform able to provide a sustained source of CXCR4-targeted pNPs that selectively accumulate in tumor cells in a CXCR4⁺ colorectal cancer xenograft model. In addition, the proposed system could be potentially adapted to any other protein construct offering a plethora of possible new therapeutic applications in nanomedicine.

In the study the researchers have generated novel smart biomaterials gathering most of the desirable features for implantable DDS, with cost effectiveness and simplicity in the biofabrication process. In this regard, single step fabricated IBs when injected subcutaneously rendered a long lasting release of targeted pNPs, able to enter to the blood stream and specifically target the tumor for as long as 10 days and they have described for the first time an approach for the fabrication of protein DDS based on protein deposition as IBs and their sustained release in form of fully functional targeted pNPs. This technology provides and stable source of targeted protein nanoparticles during long periods within the body with the action at distal points from the implantation site and pave the way for the appearance of new more efficient and less invasive treatments for a broad number of pathologies.

Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the U1. Protein Production Platform (PPP), whereas the in vivo biodistribution assays were performed in the NANBIOSIS U18. Nanotoxicology Unit,

For further information see https://sciencedirect.com/science/article/pii/S0168365918301780?via%3Dihub

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Online oxygen monitoring using integrated inkjetprinted sensors in a liver-on-a-chip system

Scientists of NANBIOSIS Unit 8. Micro – Nano Technology Unit, led by Gemma Gabriel, Scientific Coordinator of the Unit, are the authors of the article “Online oxygen monitoring using integrated inkjetprinted sensors in a liver-on-a-chip system”, published by Lab on a chip.

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of organ-on-a-chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in OOC systems increases their biological complexity and therefore makes the analysis and monitoring of analytical parameters inside the device more difficult. In this work, theauthors present an approach to integrate multiple sensors in an extremely thin, porous and delicate membrane inside a liver-on-a-chip device. Specifically, three electrochemical dissolved oxygen (DO) sensors were inkjet-printed along the microfluidic channel allowing local online monitoring of oxygen concentrations. This approach demonstrates the existence of an oxygen gradient up to 17.5% for rat hepatocytes and 32.5% for human hepatocytes along the bottom channel. Such gradients are considered crucial for the appearance of zonation of the liver. Inkjet printing (IJP) was the selected technology as it allows drop on demand material deposition compatible with delicate substrates, as used in this study, which cannot withstand temperatures higher than 130 °C. For the deposition of uniform gold and silver conductive inks on the porous membrane, a primer layer using SU-8 dielectric material was used to seal the porosity of the membrane at defined areas, with the aim of building a uniform sensor device. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes were performed, and oxygen consumption rate was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), accelerating the basal respiration of 0.23 ± 0.07 nmol s⁻¹/10⁶ cells up to 5.95 ± 0.67 nmol s⁻¹/10⁶ cells s for rat cells and the basal respiration of 0.17 ± 0.10 nmol s⁻¹/10⁶ cells by up to 10.62 ± 1.15 nmol s⁻¹/10⁶ cells for human cells, with higher oxygen consumption of the cells seeded at the outflow zone. These results demonstrate that the approach of printing sensors inside an OOC has tremendous potential because IJP is a feasible technique for the integration of different sensors for evaluating metabolic activity of cells, and overcomes one of the major challenges still remaining on how to tap the full potential of OOC systems.

Article of reference: DOI: 10.1039/C8LC00456K

This article is part of the themed collection: Organ-, body- and disease-on-a-chip systems

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Abstract