2018 - Nanbiosis

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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Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Scientists of Units 1 and 18 of NANBIOSIS are coathors of the article “Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides” published by Nanomedicine: Nanotechnology, Biology and Medicine

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV).

Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. The authors have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, they have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerizationstatus of the nanoscale material, both regulatable by conventional protein engineering approaches

Article of reference:

Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde. Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides Nanomedicine: Nanotechnology, Biology and Medicine Volume 14, Issue 6, August 2018, Pages 1777-1786

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Nanoligent obtains the first prize in the Tech Transfer Competition in the ONCO Emergence forum

Last June 21-22th, took place at the Fira Gran Via in Barcelona, the ONCO Emergence forum, a networking conference focused on setting up transnational collaboration projects in oncology by promoting interaction among research institutes, companies and medical facilities like hospitals.

In other to promote alliances and generate collaborative projects from hospitals and academia to other stakeholders, ONCO Emergence Forum Barcelona has created a Tech Transfer Competition that features cherry-picked entrepreneurs, TTO or principal investigators developing new technology ready to be licensed or in development through a spin-off. Selected participants presented their innovative projects in a 6-minute English pitch to an experienced panel of judges, being the prize €1,500, provided by Fundación Pública Andaluza Parque Tecnológico de la Salud de Granada. The competition target are therapeutic, diagnostic, medtech and digital health projects in oncology within the framework of improving healthcare and medical assistance with a deep focus on an unmet medical/market/patient need, resolved through an innovative technology to create a product or service; project must be in TLR 2-4 with tested hypothesis and demonstrated proof-of-concept as well as safety in in vitro/animal model.

NANOLIGENT, the spin off created by the Directors of NANBIOSIS Units U1. Protein Production Platform (PPP), Antoni Villaverde and U18. Nanotoxicology Unit, Ramón Mangues, together with Esther Vázquez and Manuel Rodriguez, was awarded with the First Prize.

Nanoligent´s project is about antimetastatic medication for colorectal cancer and its business model is carrying out a first clinical trial which demonstrates the efficacy of the medication in humans and allows the company to sign a license agreement with a pharmaceutical company.

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Esther Pueyo, NANBIOSIS U 27, at the 3rd Barcelona VPH Summer School

The 3rd VPH Summer School was held in Barcelona, on June 18-22, 2018. The VPH Summer School series is co-organized by the Barcelona MedTEch – Pompeu Fabra University and by the Virtual Physiological Human Institute. The Summer School provides a thorough overview and hands-on experience in state-of-the-art Virtual Physiological Human (VPH) research. The event is dedicated to PhD students and junior postdocs who seeks cross dissemination and a guided experience through the use of computer models and simulations to tackle specific clinical problems, not only engineers but also biomedical scientists and medical doctors with an interest in computer modeling and simulation for research and clinical practice. It aims to provide junior engineers and medical doctors with a complete overview of state-of-the-art VPH research, following a complete pipeline from basic science and clinical needs, to model application. The Summer School has the support of the Marie Curie ITN CardioFunXion.

This 3rd edition has focussed on data integration, model verification and validation and 16 international keynote speakers shared their research experience. Esther Pueyo, researcher of NANBIOSIS unit U27. High Performance Computing, spoke in the session of June 22nd dedicated to the subject of Understanding simulation outcomes, technological transfer, decision and therapy support: Patient-specific modeling, Interpretative machine learning, metamodeling, success and failure stories, giving a very nice presentation of experimental and numerical approaches in multiscale modelling for cardiac ageing.

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Nanoligent, the spin off created by the Directors of Units 1 and 18 of NANBIOSIS, awarded for the best company in Health Sciences given by the law firm RCD

NANOLIGENT is awarded for the best company in Health Sciences Price given by the law firm RCD.

The XXIII Investment Forum of ACCIÓ 2018 was celebrated last June 20^thwith the aim of connecting with the world of private investment. ACCIÓ, Company Competitiveness Agency, had previously published a catalog of startups with the most potential startups in Catalonia, projects selected from more than 100 candidatures were presented for the 2018 Investment Forum of ACTION. The 50 companies in this catalog stand out due to their differential nature and innovative value, due to their social impact and the involvement of the entrepreneurial team. They are companies operating in key sectors for the economy of the future such as life and health sciences, ICT and other crucial cutting-edge technologies for industry 4.0 including 3D printing, IoT and virtual reality. The 21 finalists had the opportunity to present themselves to a large number of investors and venture capital funds during the Forum’s celebration, an audience of 600 people who voted the 9 best companies to participate in the final. Nanoligent, S.L., the company stablished on March 2017 by professors Dr. A. Villaverde and Dra. E. Vázquez from NANBIOSIS Unit 1, professor Dr. M. Mangués from NANBIOSIS Unit 18, and entrepreneur Dr. M. Rodríguez won the award for the best company in Health Sciences given by the law firm RCD (Rousaud Costas Duran)

NANOLIGENT’s mission is to improve the lives of patients by designing new medications that selectively target the cells affected by disease. With this approach NANOLIGENT develops treatments that are more effective and have less adverse effects than classical drugs using state-of-the-art protein engineering and nanobiotechnology. Currently Nanoligent is working on antimetastatic medication for colorectal cancer and its business model is carrying out a first clinical trial which demonstrates the efficacy of the medication in humans and allows the company to sign a license agreement with a pharmaceutical company

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A CO2 optical sensor based on self-assembled metal–organic framework nanoparticles

Carbon dioxide (CO₂) is a known pollutant that affects the performance of humans in workplaces, schools and other indoor areas. Thus, the development of devices for sensing and monitoring CO₂ levels is crucial for many fields such as food packaging and for human safety indoors. Researchers of NANBIOSIS U4. Biodeposition and Biodetection Unit, led by Prof. Laura M. Lechuga, are co-authors of the article “A CO2 optical sensor based on self-assembled metal–organic framework nanoparticles published by Journal of Materials Chemistry A., wich shows an optical CO₂ sensor fabricated by integration of a metal–organic framework (MOF) onto bimodal optical waveguides.

The sensor showed a broad linear response, with limit of detections of 3130 ppm at room temperature and 774 ppm at 278 K; values that are below the threshold for CO₂ monitoring in food packaging and for human safety indoors. Furthermore, it is robust, selective, fast and reusable, and can be stored under humid conditions with no loss in performance. The results should enable the development of fully integrated MOF-based sensors for in situ gas sensing and other in situ practical applications.

Article reference:

Blanca Chocarro-Ruiz, Javier Pérez-Carvajal, Civan Avci, Olalla Calvo-Lozano, Maria Isabel Alonso, Daniel Maspoch and Laura M. Lechuga. A CO₂ optical sensor based on self-assembled metal–organic framework nanoparticles. J. Mater. Chem. A, 2018, Advance Article. DOI: 10.1039/C8TA02767F

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NANOMEDICINE APPLICATIONS IN DRUG DELIVERY AND TARGETING: NANBIOSIS – NANOMED Industrial Forum

Yesterday took place in Barcelona, at Barcelona School of Management, Universitat Pompeu Fabra, a meeting of resarch groups and units of NANBIOSIS and CIBER-BBN and companies in the third B2B Forum organized by NANBIOSIS, in this case together with NANOMED SPAIN.

Thirteen companies and twelve groups from CIBER-BBN and CCMIJU (ten of them coordinating NANBIOSIS units) got together to explain, through short presentations of ten minutes, those lines of their work aimed at finding synergies and potential collaborations in the area of Nanomedicine apllications in drug delivery and targeting. There was also a talk by a representative of CDTI (Spanish National Center for Industrial and Technological Development) to explain the financing opportunities for the companies as well as a presentation by the NANBIOSIS Coordinator, Jesús Izco, to show the new Cutting Edge Biomedical Solutions offered by the ICTS-NANBIOSIS.

After lunch, the groups and companies had the opportunity to discuss in more detail, during bilateral interviews coordinated by NANBIOSIS a, those aspects that had attracted their attention, as well as, in some cases, to draw potential collaborations. The event was successfully developed with 45 attendees and more than 50 individual B2B mettings.

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Infections such as Candiasis will be detected in 30 minutes

Ramón Martínez Máñez, Elena Aznar and Ángela Ribes, researchers of Unit 26 of NANBIOSIS, NMR: Biomedical Applications II, in collaboration with researchers from the Universitat Politècnica de València, with the Universitari i Politècnic La Fe Hospital and the Rovira i Virgili University, have developed a new material that allows to detect quickly and with a high sensitivity infections caused by Candida albicans, a type of fungus that can be found in different biological fluids, causing opportunistic infections such as Candidemia or Invasive Candidiasis.

According to Javier Pemán, head of section and head of the Mycology Unit of the Microbiology Service of the Hospital Universitari i Politècnic La Fe,” infections are difficult to identify early, very frequent in most Intensive Care Units (ICUs) and represent an important challenge in critical patients”.

Currently, these infections are diagnosed by culturing the biological fluid to be studied and subsequent identification of yeast isolated by different microbiological techniques whose results can take between 3 and 4 days. Meanwhile, with this new material and method – patented by the UPV, the CIBER, the Hospital La Fe and the URV – the diagnostic time is reduced to only 30 minutes.

“The tests can be carried out quickly and practically in the same consultation in which the patient sample is taken, significantly reducing the equipment necessary to detect the presence of Candida albicans. Our work facilitates the diagnosis and medical decision-making, through the use of a powerful and fast tool to detect the infection”, says Ramón Martínez Máñez, scientific director of the CIBER-BBN and director of the IDM Institute at the UPV, as well as scientific director of NANBIOSIS U26.

Nanoporous films with molecular doors

The material developed by the CIBER-BBN research gourp, led by Ramón Martínez Máñez, is about nanoporous alumina films that incorporate “molecular doors” based on oligonucleotides. The characterization has been carried out in Unit 26 of NANBIOSIS, NMR: Biomedical Applications II.

“They are constituted by a porous inorganic support that is loaded with a dye and by simple strands of DNA. These strands are anchored to the surface of the support and act as “molecular doors” that inhibit the release of the indicator “, explains Ramón Martínez Máñez.

In addition, according to Professor Lluis Marsal, from the Rovira i Virgili University, the type of support used greatly simplifies the methodology of the experiment.

On how to detect the infection, Professor Martínez Máñez explains that the simple strands of DNA are selected taking into account a specific sequence of Candida albicans.

“When the presence of the DNA of this fungus is noticed, it interacts with the molecular door, the pores open and that is when the release of the dye that is inside the nanoporous support takes place, thus detecting the infection,” adds Elena Aznar , researcher of the CIBER-BBN in the IDM-UPV.

The diagnostic material is now in the clinical validation phase, thanks to the funding obtained through the CANDI-GATE project granted by the Polytechnic University of Valencia and the La Fe Health Research Institute and led by M. Angeles Tormo and Elena Aznar and through the CANDI-EYE valuation project granted by the CIBER-BBN and led by Elena Aznar.

Patent of reference:

“Porous material for the detection of Candida albicans, diagnostic method that uses it and method of preparation of it”. Spanish application pattent P201731069 2017-09-05.

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NANBIOSIS working on the development of next generation catheters

NANBIOSIS’ partners CIBER-BBN and JUMISC, with another 44 European partners, led by Philips Electronics Nederland B.V, will work on the development of next genration catheters.

The project, Position-II (Ref. n. 783132), that pretends to diversify the production of smart catheters (overcoming the obsolescence of current ones), improve their performance (facilitating their use to be smaller), reduce current production costs and break existing monopolies, has been submitted to the Call for Electronic Components and Systems for European Leadership (ECSEL)- Horizon 2020, with a duration of three years -starting on 1/6/18- and with a budget of over €41M, (€10.4M-financed by European Union)

The objective of the participation of JUMISC in Position-II is to develop new catheters that, in combination with hydrogels and cell therapy, will have a regenerative effect to stimulate the recovery of cardiac areas damaged by heart attacks. NANBIOSIS U10. Drug Formulation, of CIBER-BBN, at UPV-EHU, coordinated by José Luis Pedraz and Jsús Ciriza, will microencapsulate the cells to be test and administered in porcine model at the JUMISC to validate the designed catheter.

The kick-off of the Eurpean project under Grant Agreement Ecsel-783132- POSOTION II 2017-IA took place on June 5 to 7 in Rotterdam, representatives of the NANBIOSIS-ICTS Steering Committee, unit 10 and unit 24 were present.

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Nanoporous films with molecular doors