News

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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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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