News U6

A step forward for the design of multifunctional protein nanomaterials for cancer therapies

Researchers of NANBIOSIS Unit 1 and NANBIOSIS Unit 18, led by Prof Antoni Villaverde have published the article at the prestigious scintific magazine titled Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer

The researchers have shown that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies.

Protein production has been partially performed by the ICTS NANBIOSIS U1, Protein Production Platform and the nanoparticle size analysis by the U6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit. Biodistribution studies were performed by the U18 of the ICTS NANBIOSIS, Nanotoxicology Unit.

Article of reference:

Rita Sala, LauraSánchez-García, Naroa Serna, María Virtudes Céspedes, Isolda Casanova, Mònica Roldán, Alejandro Sánchez Chardig, Ugutz Unzueta, Esther Vázquez, Ramón Mangues, Antonio Villaverde. Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer. Acta Biomaterialia, 99, Pages 426-432. 2019,

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Why the poor biodistribution so far reached by tumor-targeted medicines?

Cell-selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor-mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self-assembling, protein-only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine-based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4+ colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell-targeted delivery requires not only the incorporation of a proper ligand that promotes receptor-mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue.

The concept presented by the authors of the present research might represent a convincing explanation of the poor biodistribution so far reached by tumor-targeted medicines, including antibody-drug conjugates. In addition to this, they offer a potential developmental roadmap for the improvement of these drugs, of high intrinsic therapeutic potential, to reach satisfactory efficiencies in the clinical context.

Hèctor López-Laguna, Rita Sala, Julieta M. Sánchez, Patricia Álamo, Ugutz Unzueta, Alejandro Sánchez-Chardi, Naroa Serna, Laura Sánchez-García, Eric Voltà-Durán, Ramón Mangues, Antonio Villaverde and Esther Vázquez. Nanostructure Empowers Active Tumor Targeting in Ligand-Based Molecular Delivery. Part. Part. Syst. Charact. 2019.

DOI: 10.1002/ppsc.201900304

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NANBIOSIS expertise on Nanoparticles Characterization by Amable Bernabé.

Amable Bernabé, Technical Coordinator of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit has given a course from Monday, 7 October, to Wednesday, 9 October on “Characterization techniques for particulate materials”. The course has counted with 12 participants from different CSIC centers (including ICMAB, IBM-CNM, ICM, IQAC…) and has introduced the participants to different techniques to characterize nanoparticles and other particulate matter, including the basic fundamentals, sample preparation, practical examples and results interpretation.

It is the second time that Amable Bernabé, technician from the Sof tLab, has decided to offer this course to all the CSIC community, so they can learn new methods to characterize nanoparticles, the theory behind the techniques, and how to manage the equipment.

Specifically, the techniques shown are:

Theory:

Dynamic Light Scattering (DLS) with Zetasizer Nano ZS (Malvern Instruments)
- Size distribution
- Z Potential
Nanoparticle Tracking Analysis (NTA) with Nanosight NS300 (Malvern Instruments)
- Size distribution
- Particle concentration
- Fluorescence
Light Scattering (LS) with Mastersizer 2000 (Malvern Instruments)
- Size distribution

Practice:

Sample analysis and practical cases of Dynamic Light Scattering with the Zetasizer Nano ZS (Malvern Instruments) equipment.
Samples analysis and practical cases of the Nanoparticle Tracking Analysis (NTA) technique with the Nanosight NS300 (Malvern Instruments) equipment.
Sample analysis and practical cases of the Light Scattering (LS) technique with the Mastersizer 2000 (Malvern Instruments) instrument.

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NANBIOSIS Scientific Director, Jaume Veciana, coauthor of an article highlighted in Chemistry Views

Jaume Veciana, Scientific Director of NANBIOSIS is coauthor of an article chosen to be highlighted on the ChemistryViews newsletter: “Organic Free Radicals as Circularly Polarized Luminescence Emitters”, published in Angewandte Chemie International Edition, and is about the intrinsic chiral emission of enantiometric organic free radicals.

The short news about the paper is entitled “Circulary Polarized Light from Organic Radicals” is available here.

Circularly polarized luminescence (CPL) can occur when a luminescent compound has a chiral structure. Organometallic structures are leading in CPL activity. However, purely organic CPL emitters are promising alternatives in several applications where low toxicity is important
(i.e., bioimaging).

Jaume Veciana (Institut de Ciéncia de Materials de Barcelona (ICMAB), Spain), Araceli G. Campaña (University of Granada, Spain) and colleagues have found a new approach for the optimization of organic emitters with intrinsic chirality. In particular, tris(2,4,6-trichlorophenyl)methyl (TTM) and perchlorotriphenylmethyl (PTM) radicals, which both have a chiral propeller-like shape, were used. In addition to their chirality, these materials are magnetically active. They are also easy to modify in order to optimize their properties.

The team separated the two racemic compounds into their enantiomers using chiral stationary phase high-performance liquid chromatography (HPLC). The CPL spectra of the four resulting fractions (examples pictured) were recorded and the researchers found highly efficient chiral emission for both pairs of enantiomers. According to the researchers, this is the first time results about the intrinsic chiral emission from enantiomeric organic free radicals have been reported. The work might be a starting point for the development of improved chiral organic radical emitters.

Reference article:Organic Free Radicals as Circularly Polarized Luminescence Emitters
Paula Mayorga Burrezo, Vicente G. Jiménez, Davide Blasi, Imma Ratera, Araceli G. Campaña, Jaume Veciana,
Angew. Chem. Int. Ed.2019.
https://doi.org/10.1002/anie.201909398

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Biomarkers in semen to diagnose prostate cancer

Sara Larriba of the Human Molecular Genetics Group of Bellvitge Biomedical Research Institute (IDIBELL) has informed NANBIOSIS about a recent publication mentioning NANBIOSIS in the Acknowledgements for its participation in the results of their research. (The nanoparticle tracking analysis was performed by the ICTS NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit) The article has been published by the journal Scientific Reports of Nature Research.

The prediction of PCa in the early stage of the disease is one of the most important objectives in male urology. A significant decrease in deaths due to PCa has been associated with the use of serum PSA test recent years. However, the PSA test still has serious limitations and often gives false positives that lead to many unnecessary biopsies of benign disease. Therefore, researchers from the Human Molecular Genetics Group of Bellvitge Biomedical Research Institute (IDIBELL) decided to evaluate semen as a source of prostate cancer biomarkers, and studying extracellular miRNAs, which are present within semen in extraordinary concentrations since some of the Some of these extracellular miRNAs are specific to the prostate gland and, in addition, there is already research showing that extracellular miRNAs can reflect altered patterns of miRNA expression in prostate tumor tissue. The study conducted allowed scientists to discover a distinctive miRNA expression pattern in exosomal semen samples obtained from men with prostate cancer compared with that found in exosomal semen samples taken from healthy men. The next step would be to conduct more prospective studies in larger patient cohorts before this miRNA-based biomarker can be adopted in daily clinical practice.

Article of reference:

Semen miRNAs Contained in Exosomes as Non-Invasive Biomarkers for Prostate Cancer Diagnosis, Maria Barceló, Manel Castells, Lluís Bassas, Francesc Vigués2 & Sara Larriba. Scientific Reports volume 9, 24 Sept 2019.

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Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies

Three units of NANBIOSIS have collaborated in obtaining the research results published in the article “Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies” published by Advanced Science

Protein production and DLS have been partially performed by the Unit 1 of ICTS NANBIOSIS Protein Production Platform (PPP) and the Unit 6 NANBIOBIS Biomaterial Processing and Nanostructuring Unit. Biodistribution and immunohistochemistry assays were performed at NANBIOSIS U20 In Vivo Experimental Platform/FVPR

Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44‐targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44⁺ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.

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New publication by scientists of NANBIOSIS Unit 6 aims to motivate scientific community to start a new research line for organic and bio-organic electronics focused on the device fabrication

Researchers of Nanomol Group, coordinator of NANBIOSIS U6 of CIBER-BBN and ICMAB-CSIC, led by Inma Ratera and Jaume Veciana have publish a new article titled “Reversible switching of the Au(111) work function by near infrared irradiation with a bistable SAM based on a radical donor–acceptor dyad“, at Journal of Materials Chemistry C.

Article:
https://pubs.rsc.org/en/content/articlelanding/2019/TC/C9TC00906J#!divAbstract

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Nanomol group initiates contact with the AEMPS to bring a new treatment against venous leg ulcers to the clinic

Researchers of the Nanomol group, ICMAB-CSIC and CIBER-BBN members of the ICTS “NANBIOSIS”, specifically of the Biomaterial Processing and Nanostructuring unit (U6), together with the company Nanomol Technologies S.L. have begun a consultation process with the Spanish Association of Medicines and Health Products (AEMPS) to try and enter a new treatment in a clinical studies stage, to fight against venous ulcers in lower extremities. The study is carried out within the framework of the RIS3CAT NANONAFRES project.

Approximately, 80% of ulcers in lower extremities have associated pathologies of venous insufficiency and these wounds are usually recurrent. An open ulcer can take from weeks to years to close, increasing the risk of mortality and affecting the quality of life of patients who suffer from them, mostly elderly people. The solution proposed within the NANONAFRES project consists of a medicine for topical application based on the incorporation of a biomolecule, with skin regenerating activity, encapsulated in nanoparticles. This approach ensures the protection of the active substance, preventing its degradation, while allowing the controlled and direct release of the drug in the area of the ulcer.

The NANONAFRES project, led by Nanomol Technologies SL, was born from the collaboration of the Nanomol group from ICMAB-CSIC with the companies Nanomol Technologies and BIOMED-LEITAT, the primary care centres EAP Osona Sur-Alt Congost SLP and the EAP Vallcarca-Sant Gervasi, public hospitals such as the Terrassa Health Consortium and the Maresme Health-Consortium Foundation and international research centres such as the Centro de Ingeniería Genética y Biotecnología de Cuba. This project, awarded with a RIS3CAT fund sponsored by the Generalitat of Catalonia, has a budget of 2.3 million euros and a duration of 3 and a half years.

This first consulting meeting with the AEMPS is a very important milestone in the process of developing any drug, in order to carry out clinical trials and transfer the system to the market, and thus bring the proposed treatment to the people who need it.

This approach will improve the effectiveness of current venous ulcers treatments, as well as the quality of life of patients, reducing the cost of medicines available today. In addition, the Nanomol group already has an internationally granted patent on this product, which demonstrates the novelty of this system and strengthens its position to reach the market through the partners present in this consortium and, in particular, through its spin-off Nanomol Technologies S.L.

Links of interest:

Article published on ICMAB’s site: http://icmab.es/nanomol-participa-al-projecte-nanonafres-de-la-comunitat-ris3cat-de-nous-dispositius-de-diagnostic-i-big-data-aplicades-a-la-salut

Article published on LEITAT’s site: https://projects.leitat.org/nanonafres/

Patent: “VESICLES COMPRISING EPIDERMAL GROWTH FACTOR AND COMPOSITIONS THEREOF” (WO2014019555)

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Judit Tomsen: Best oral presentation at ESC 2019

Last June 18-22 at the 2019, ESC meeting, the European Students Colloid Conference, that took place in Varna, Bulgaria, Judit Tomsen, PhD fellow at the Nanomol group from CIBER-BBN and ICMAB-CSIC, was awarded with the best oral presentation.

Judit Tomsen, who carries out her work under supervision of Nora Ventosa, Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit, presented her oral communication entitled “Design of peptide targeted nanovesicles for the α-galactosidase A enzyme delivery“. Her talk explained some of the smart4fabry european project results, a project coordinated by CIBER-BBN and Nora Ventosa in which participates NANBIOSIS Unit 6.

The European Colloids and Interfaces Society (ECIS) organizes biannually ESC meetings of advanced students at PhD and MSc level who are undertaking research in the area of colloid and interface science at a European University.

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Mechanism of interaction of a material (pharmaceutical, food, construction, chemical, etc.) with moisture or with any organic vapor.

Next June 11, 2019, from 09:30h to 17:00h, will take place in Eureka Building – Parc de Recerca, UAB (Barcelona), a Scientific-Theoretical / Practical Workshop on: DYNAMIC SORPTION OF VAPORS (DVS – DYNAMIC VAPOR SORPTION) AND CHARACTERIZATION OF MATERIALS (iGC / SEA – INVERSE GAS CHROMATOGRAPHY / SURFACE ENERGY ANALYZER) FOR THE ANALYSIS OF THE SORTION OF WATER AND ORGANIC VAPORS, AND CHARACTERIZATION OF MATERIALS AND SURFACES.

The event is organized by IESMAT, S.A. in collaboration with Nanomol Technologies SL, the Institute of Materials Science of Barcelona (ICMAB-CSIC), Surface Measurement Systems (SMS) and the Center for Biomedical Research in Network (CIBER)/NANBIOSIS, includes theoretical presentation DVS (Dynamic Vapor Sorption) technologies and iGC-SEA (Inverse Gas Chromatography – Surface Energy Analyzer).

This workshop, addressed to researchers and/or technicians interested in knowing the mechanism of interaction of a material (pharmaceutical, food, construction, chemical, etc.) with moisture or with any organic vapor, and DVS users, includes: Presentation of equipment and instrumentation of Surface Measurement Systems (SMS) distributed by Specific Instrumentation of Materials (IESMAT). Presentation of users of dynamic vapor sorption equipment. Demonstration of hardware and software of the DVS Intrinsic equipment.

FREE REGISTRATION– until full capacity is reached. To formalize it, contact Ms. Estefanía Écija (estefania.ecija@iesmat.com; 91 650 8005), before June 6th, indicating name, company, telephone and e-mail.

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Specifically, the techniques shown are:

Theory:

Practice: