News U18

NANBIOSIS Against Cancer

The World Health Organization, the International Cancer Research Center (IARC) and the International Union Against Cancer (UICC) celebrate February 4 of each year as World Cancer Day

Every year, 14 million new cases of cancer are diagnosed worldwide and the disease causes 8.2 million deaths.

Thanks to scientific research, great advances have been made in the fight against cancer. Through surgery, chemotherapy or radio therapy and, in the last 20 years, through immunotherapy, hormonal treatment or cell therapies, tools have been obtained to improve early diagnosis and treatments, increasing cancer survival by 20%.

The only way to understand cancer and, someday, eradicate it or eliminate the suffering and death due to this disease, is RESEARCH

NANBIOSIS as an ICTS (Singular Scientific and Technical Infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples are bellow:

Thanks to a coordinated action between units U1 of Protein Production Platform (PPP), U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, NANBIOSIS is developing nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer, by using of proteins with high specificity of binding to metastatic cells and a high degree of permanence in the blood flow, loaded with anti-cancer drugs that are selectively released inside the tumor cells that are going to form the metastases. Through the public financing of a NEOTEC project and a RETOS-COLABORACION and the company NANOLIGENT SL, the first antimetastatic drug on the market will be developed.

The Protein Production Platform-PPP collaborates with research projects whose objective is the development of new cancer therapies based on recombinant modular proteins with the ability to self-assemble. These multimeric complexes have shown, in animal models, a high stability in serum and an improved biodistribution compared to that observed with drugs for clinical use. These principles have been valued in different types of cancer, including colorectal cancer and breast cancer. The modular design of these constructions allows the incorporation or substitution of direct peptides and therefore they are presented as a transversal tool for more effective treatments against cancer. In addition, the PPP has served the Vall d’Hebron Institute of Oncology (VHIO) of Barcelona, the Josep Vilanueva group (CIBERONC) in the field of biomarker study and new targets associated with triple negative breast cancer (TNBC).

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit is working on a project in collaboration with VHIR, financed by the Spanish Goverment and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

Unit 6 is also working on the project Artificial Lymph Nodes for Cancer ImmunoTherapy (ALYCIA) A project born of a initiative of CIBER-BBN/ CIBERONC to enhance scientific interdisciplinary collaborations between research groups working on oncology and nanomedicine. Researchers of unit 6 will develop Artificial Lymph Nodes (ALN) based on dynamic 3D scaffolds able to promote efficient ex vivo lymphatic cell expansion of relevant phenotypes. Such ALN represent a new approach to lymphocyte expansion, which not only includes artificial Antigen Presenting Cells in suspension like the state-of-the-art expansion techniques, but also mimics the function of the LN ex vivo.

One of the singular capabilities of the U25 of NANBIOSIS NMR: Biomedical Applications I is the acquisition of high quality, high resolution preclinical magnetic resonance imaging/spectroscopy/spectroscopic imaging data. This allows performing leading-edge studies in preclinical cancer models such as noninvasive therapy response follow-up in murine brain tumours, revealing new response biomarkers with translational potential for brain cancer patients.

NANBIOSIS U4 Biodeposition and Biodetection Unit is currently developing the national project PREDICT Point-of-care Nanoplasmonic Platforms for Novel High-Value Diagnostics and Therapy Follow-Up , which works in the early detection of lung cancer. PREDICT project will use the Unit 4 of Nanbiosis for the multiplexed biofunctionalization of the biosensor chips and their methodology optimisation.

Finally, Unit 20 of NANBIOSIS In Vivo Experimental Platform at VHIR, is the most implicated of the CIBER units on projects in the field of cancer, just to name some of them: H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells. FIS-ISCIII: polymeric micelles for siRNA and combined therapy against breast cancer tumor stem cells. CarboXigel: hydrogels for the sustained release of chemotherapeutic drugs against the metastatic spread of ovarian cancer. MelanoMir: nanomedicine applied to skin cancer, melanoma, beside other projects promoted by CIBER-BBN.

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A new pathway for the prevention of metastasis in colorectal cancer in humans is open: a nanomedicine that selectively eliminates metastatic stem cells

Researchers of NANBIOSIS U18 Nanotoxicology Unit and U1. Protein Production Platform (PPP) at the Biomedical Research Institute of Sant Pau (IIB Sant Pau), of the Hospital of Santa Creu i Sant Pau, of the Universitat Autònoma de Barcelona (UAB), the Superior Council of Scientific Research (CSIC) and the Center for Biomedical Research in Network (CIBER) have published an article in one of the most prestigious international scientific journals in the field of Molecular Medicine, EMBO Molecular Medicine. This article demonstrates the efficacy of the nanopharmaceutical that selectively removes metastatic stem cells in animal models of colon cancer. The new drug works like a drone that has a ligand that identifies a receptor (CXCR4) in the metastatic stem cells, administers the drug and destroys these cells by blocking the metastasis. The drug acts only on metastatic tumor cells and not on healthy cells, so it avoids the general toxicity associated with the usual treatments

This nanopharmaceutical has been successfully tested in animal models of colorectal cancer, but could be used in 20 additional tumor types that express CXCR4,
as in those of prostate, breast, ovary and others

This is the first drug in the world selectively antimetastatic that addresses the medical need to block metastatic spread, the main cause of death in cancer patients, while eliminating the toxicity and adverse effects of conventional treatments

The Hospital de Sant Pau could be the first center in the world to carry out clinical trials that evaluate this new drug in patients, prior to its possible introduction in clinical therapeutics

It has been observed that this receptor is overexpressed in at least 20 different types of cancer, including those of the prostate, breast, ovary and others not as common as the pancreas. This means that this nanoparticle can be targeted to treat different types of neoplasms, making it a very versatile vehicle that can transport different therapeutic molecules of high potency.

Article of reference:

María Virtudes Céspedes, Ugutz Unzueta, Anna Aviñó, Alberto Gallardo, Patricia Álamo, Rita Sala, Alejandro Sánchez‐Chardi, Isolda Casanova, María Antònia Mangues, Antonio Lopez‐Pousa,Ramón Eritja, View Antonio Villaverde, Esther Vázquez, Ramón Mangues. Selective depletion of metastatic stem cells as therapy for human colorectal cancer. EMBO Molecular Medicine (2018) e8772 Published online 06.09.2018. DOI 10.15252/emmm.201708772

The team of researchers, led by Dr. Ramón Magues de l’IIB Sant Pau, Prof. Antonio Villaverde of the UAB and Dr. Esther Vázquez of the UAB, have shown that the drug acts only on metastasis-initiating cells through its specific interaction between a peptide present in the protein nanoparticle that transports it and the cellular receptor CXCR4 that is overexpressed in tumor cells. This allows attacking only the tumor cells, blocking their dissemination in early stages, in a way that prevents the appearance of metastasis while avoiding the adverse effects derived from the usual treatments.

Nanoligent, a new spin-off to finance the nanoparticle

In June 2017, researchers from the IIB Sant Pau, from the Institute of Biotechnology and Biomedicine of the UAB and the CIBER from Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) who signed the article published now in EMBO Molecular Medicine created a spin-off, Nanoligent , with the aspiration to develop the first drug designed to eliminate metastatic cells.

This company, which has more than 10 years of studies behind it, is directed by Dr. Manuel Rodríguez Mariscal, a professional with a long experience in the field of investment and the creation of biotechnology companies and aims to obtain financing for the realization of the project.

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Nanoparticle uptake and in vivo estimates of therapeutic efect and toxicity

Ramón Mangues, Scientific Dierctor of unit 18 of NANBIOSIS, Unit of nanotoxicology, explains in this video some of the animal models used in the unit for preclinical validation of nanoparticles, especially of application in cancer

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The general consul of France meets with NANBIOSIS researchers

The general consul of France in Barcelona, Mr. Cyril Piquemal visited the IBB UAB facilities last July 18, to find out about the research that is being carried out and, in particular, explore possible collaborations in nano-pharmacy development projects.

During the visit, the Consul of France in Barcelona was received by Màrius Martínez, Vice President of International Relations at the UAB; Maite Paramio, Deputy Vice President; Ivan Martínez, vice president of Research; Salvador Ventura, director of the Institute of Biotechnology and Biomedicine, and Antonio Villaverde, head of the IBB Nanotechnology Unit-NANBIOSIS U1. Protein Production Platform (PPP)

Next, the mayor visited the facilities and laboratories of the Institute and met with the researchers Esther Vázquez and Antonio Villaverde, (NANBIOSIS U1. Protein Production Platform (PPP)), and Ugutz Unzueta and Ramón Mangues, (NANBIOSIS Unit 18 Nanotoxicology Unit) at the Institute of Research of the ‘Hospital de la Santa Cruz and San Pablo, to find out about the research in the development of nanoparticles for metastases treatment by means of the selective elimination of tumor stem cells.

In addition, the researchers explained to the consul the case of the spin-off Nanoligent, to show a project born from the research and whose objective is to develop the first selective drug to treat metastasis

The purpose of the meeting was to explore possible collaborations between the University and the Consulate, an entity that aims to connect research groups and venture capital funds with the Catalan biotechnology ecosystem.

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Nanomedicine to fight against the spread of cancer

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 is highlighted in la Vanguardia.

More information here

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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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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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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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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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