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Posts Taged drug-delivery

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Nano-carrier to release drugs into damaged cells

Senescent cells are damaged cells that do not perform their normal roles anymore but that are not dead –hence they are commonly known as zombi cells. These cells interfere with the functioning of the tissue in which they accumulate. Senescence is a cell program that is triggered by many types of damage and senescent cells are present in many diseases. They accumulate in diverse types of tissues during aging, thus contributing to the progressive deterioration associated to aging. Eliminating these zombi cells is one of the challenges facing science today.

In the Cellular Plasticity and Disease lab headed by the ICREA researcher Manuel Serrano at the Institute for Research in Biomedicine (IRB Barcelona) and supported by “la Caixa” Banking Foundation, the researchers devise strategies to eliminate senescent cells. In a study published in EMBO Molecular Medicine, they present a proof of principle of a drug delivery system with selectivity for tissues that harbour senescent cells.

In collaboration with a team headed by Ramón Martínez-Máñez, Scientific Diirector of NANBIOSIS Unit 26 NMR: Biomedical Applications II ,  the IRB Barcelona scientists have exploited a particular hallmark of senescent cells in order to design a delivery system that specifically targets them. They have demonstrated its efficacy in cells in vitro and in two experimental mouse models, namely pulmonary fibrosis and cancer. These diseases are characterized by the presence of damaged cells, and in the case of cancer this is particularly true after treatment with chemotherapy.

In these models, the senescent cells take up the carrier more efficiently than other cells and once inside the cell the casing of the carrier degrades to release the drug cargo. When the nano-vehicles contained cytotoxic compounds, the senescent cells were killed and this resulted in therapeutic improvements in mice with pulmonary fibrosis or with cancer.

“This nano-carrier may pave the way for new therapeutic approaches for serious conditions, such as pulmonary fibrosis or to eliminate chemotherapy-induced senescent cells,” explains Manuel Serrano. Another outcome of this study is that these nano-carriers could be used for diagnostic tests of senescence as they can transport a fluorescent compound or marker.

This study, performed by IRB Barcelona in collaboration with the Universidad Politécnica de Valencia, CNIO, the University of Cambridge, CIBER-BBN, and the company Pfizer in the US, is a step towards achieving the capacity to eliminate senescent cells. Developing tools to specifically eliminate senescent cells is currently a central goal for many pharmaceutical companies, among them the one set up by Manuel Serrano himself together with Ramón Martínez-Máñez and José Ramón Murguia, Senolytic Therapeutics, which is located at the Barcelona Science Park and in Boston.

The study has been funded by “la Caixa” Banking Foundation, the Botín Foundation, the European Research Council, CRUK Cambridge Centre Early Detection Programme, the Ministry of Economy and Competitiveness/ERDFs and the Catalan Governmen

Daniel Muñoz‐Espín, Miguel Rovira, Irene Galiana, Cristina Giménez, Beatriz Lozano‐Torres, Marta Paez‐Ribes, Susana Llanos, Selim Chaib, Maribel Muñoz‐Martín, Alvaro C Ucero, Guillermo Garaulet, Francisca Mulero, Stephen G Dann, Todd VanArsdale, David J Shields, Andrea Bernardos, José Ramón Murguía, Ramón Martínez‐Máñez, Manuel Serrano A versatile drug delivery system targeting senescent cells EMBO Molecular Medicine (2018) DOI 10.15252/emmm.201809355

Image: The figure shows two views, frontal and lateral, of the image obtained by CT of the lungs of a mouse with fibrosis (grey areas) before and after receiving nano-therapy directed at senescent cells. (Guillem Garaulet and Francisca Mulero, CNIO)

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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

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,

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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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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NANBIOSIS organizes a forum for researchers and companies. Dates (probably February 2018) and location (probably Madrid) will be announced soon.

NANBIOSIS organizes a forum for researchers and companies. Dates (probably February 2018) and location (probably Madrid) will be announced soon.

The theme of the Forum is INTELLIGENT BIOMATERIALS / FUNCTIONALIZATION AND BIOMEDICAL DEVICES FOR APPLICATIONS IN REGENERATIVE MEDICINE AND DRUG DELIVERY.

The forum is presented through 2 sessions:

• First session: Short interventions of the latest advances and developments in the lines of research developed by the groups and platforms of Nanbiosis and description of the needs and demands of industry in that area. The companies and groups that request it will be able to have about 10 ‘to present their lines of research and / or needs and demands in relation to the thematic of the forum.
• Second session: Bilateral company-group / platform meetings to identify possible collaborations. These meetings will be pre-scheduled on request.

If you are interested in participating, contact Eduard Farré (628.943.198, efarre@arvor-ing.com) or with Jesús Izco (679.490.537, jmizco@ciber-bbn.es).

 

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Government of Aragón, Spain, paid tribute to the seven scientists who have a grant of European excellence and develop their projects at the University of Zaragoza: Jesús Santamaría, Diego Gutierrez, Igor Irastorza, Esther Pueyo, Manuel Arruebo, José Manuel García Aznar and Jesús Martínez de la Fuente.

President of the Government of Aragon, Javier Lambán, has personally expressed his gratitude and appreciation for the work of seven researchers from the University of Zaragoza who have been granted with projects of excellence funded by the European Research Council.

Jesús Santamaría, Scientific Director of Unit 9 of NANBIOSIS, with an Advanced Grant funded with 1.85 million euro, is working on a project to develop a microreactor that enables the industry to save energy and raw materials.

Esther Pueyo, member of the research group BSICoS of CIBER-BBN, which coordinates Unit 27 of NANBIOSIS, has a Starting Grant of 1.5 million and is studying the aging of the heart to propose new markers of risk for arrhythmias in the aging population.

Manuel Arruebo member of the research group Nanostructured films and particles of CIBER-BBN, which coordinates Unit 9 of NANBIOSIS, with a Grant Consolidator 1.5 million for the project Nanohedonism, develops injectable nanoparticles created with microfluidic reactors for the controlled and remote delivery of drugs in the treatment of chronic pain.

 

Nanbiosis_U27_U9_Three researchers of NANBIOSIS among the seven Aragonese scientists granted with an ERC.
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Ramon Martinez Mañez, Scientific Director of Unit 26 of NANBIOSIS, has participated in the development of  new nanodevices that allow the controlled release of drugs, namely doxorubicin, for therapies against breast cancer.

So far, the work has focused on cellular assays, with positive results, that could open new ways to improve the effectiveness of some drugs used in the treatment of breast cancer.

The main novelty of these nanodevices is that the molecule covering the nanodevice not only controls when the transported drugs are released, but also controls where they are released to direct them to cells expressing TLR3, a protein of the innate immune system overexpressed in some cell lines of breast cancer. Through this protein it is also launched a death signal that ends with the tumor cell.

Their study was published last January in Chemistry-A European Journal:

Ultimo A, Giménez C, Bartovsky P, Aznar E, Sancenón F, Marcos MD, Amorós P, Bernardo AR, Martínez-Máñez R, Jiménez-Lara AM, Murguía JR.Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells. Chemistry. Chemistry – A European Journal. DOI: 10.1002/chem.201504629

Nanbiosis_U26_New nanodevices to improve therapy for breast cancer
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The Scientific Director and the Coordinator of NANBIOSIS, Jaume  Veciana and Jesús Izco, were invited by Professor Stefano Geuna (Professor of Human Anatomy at the Department of Clinical and Biological Sciences of the University of Torino) last 9th of March 2016 to present the CIBER-BBN, its scientific program and  its technologies to researchers of l’Università di Torino, in order to explore the possibilities of collaboration between the two institutions and promoting joint projects.

The meeting took place at the Molecular Biotechnology Center of the Molecular Biotechnology and Health Science department (www.mbc.unito.it/en ). The audience was made up of members representing six departments such as Department of Molecular Biotechnology and Health Sciences, Department of Neurosciences or the Department of Medical Sciences among others. After the presentations, up to ten face to face meetings were organized with research groups and staff of the Internalization Office from different departments to look for synergies and find out ways of collaboration. Topics such as nanoencapsulation for drug delivery, functionalization of biomaterials for regenerative medicine, especially for nerve regeneration or cell therapy for cancer were discussed and many common interests were detected. Following up the meeting, several actions were agreed and some of them have been already initiated to start new collaborations between both institutions.

L’Università di Torino is actively developing biotechnologies in the field of biomedical sciences, with specific focus on the study of the molecular mechanisms at the basis of physiopathological processes that have a great impact on human health, such as cardiovascular diseases, inflammation, stem cell biology and cancer. These researches are based on experimental work carried out by the biomedical departments of l’ Università di Torino.

Nanbiosis U6_Partnering opportunities with l’Università degli studi di Torino 9March2016
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CIBER-BBN, partner in the DRIVE project to develop biomaterials and Cell based treatments for diabetes

The CIBER-BBN is partner in a new EU consortium which receives €8.9 million funding to develop materials and cell based treatments for diabetes

Programme of research will be a game-changer for people with Type 1 diabetes and insulin-dependent Type 2 diabetes

Last June took place in Brussels the kick-off meeting of the European project DRIVE (Diabetes Reversing Implants with enhanced Viability and long-term Efficacy), consortium involves fourteen partners from seven European countries, has received €8.9 million funding as part of the Horizon 2020 – Research and Innovation Framework Programme.

The DRIVE programme will develop natural materials and new surgical devices to enhance the transplant and survival of insulin producing pancreatic islets for the treatment of diabetes. DRIVE project is co-ordinated by Dr. Garry Duffy, Department of Anatomy and Tissue Engineering Research Group, Royal College of Surgeons in Ireland. Prof. José Luis Pedraz, led of the Nanobiocel Group of CIBER-BBN in the Universidad del País Vasco (UPV/EHU) and coordinator of the Unit 10-Drug Formulation of NANBIOSIS, participates in this consortium.

Drive Project kick-off meeting

Drive Project kick-off meeting

Diabetes mellitus is a chronic disease characterised by high blood sugar (glucose).  If not treated carefully, diabetes causes several debilitating side effects including heart disease, damage to the eyes, kidneys and nerve endings (e.g. hands, feet) and can lead to premature death. The total number of people living with diabetes in Ireland is estimated to be over 225,000.  According to the international diabetes federation (IDF), 382 million people worldwide have diabetes and in 2013 an estimated 5.1 million deaths were attributable to the disease, representing 8.4% of global adult mortality. Blood glucose is high in diabetes because of the inability of the pancreas to produce sufficient insulin, a hormone that controls blood sugar. Currently the main treatment for diabetes is the daily injection of insulin. In patients where control is poor, transplantation of pancreatic cells (which contain insulin-producing β-cells) is possible. However there are challenges with this therapy including the short supply of donor pancreases, the need to use 3-4 pancreases to get enough β-cells for treatment and poor graft survival and retention at the transplant site.

The DRIVE consortium will address these challenges by developing a completely new system to deliver pancreatic β-cells effectively in a targeted and protected fashion. This will mean that fewer donor pancreases are needed for cell transplantation allowing more patients to avail of a more effective longer-lasting treatment with less demand on donor pancreases. Additionally, the consortium will investigate the combination of DRIVE’s technology with future stem cell-derived β-cells that will widen the availability of islet transplantation therapy to all insulin-dependent patients.

Dr. José Luis Pedraz, commented on the research funding: “We are delighted to participate in the DRIVE programme to translate new collaborative research for the benefit of patients with diabetes mellitus.  Regenerative medicine and stem cell therapies have the potential to revolutionise the treatment of patients who have diabetes, and through DRIVE we will develop new technologies to enhance stem cell therapies for these patients by increasing targeting and ease of delivery using advanced biomaterials.”

DRIVE’s β-System consists of a β-Gel, which contains the pancreatic β-cells within a pancreas mimicking gel; which itself is protected within a capsule called a β-shell. This is delivered using a specialised injection catheter, called β-cath, which offers a more minimally invasive surgical procedure than is currently used.

The current transplantation technique offers patients natural glucose control for 1-2 years. DRIVE’s β-system aims to provide control for up to 5 years by increasing the longevity of the β-cell transplant. The system offers further advantages through the slow release of immunosuppressant drugs by the β-shell, reducing the patient’s need for long-term anti-rejection medication, which has harmful side effects. The β-shell will also be retrievable, so it can be removed and replenished after the 5-year period. DRIVE’s 5-year work plan will include animal testing, with a view to human testing at the end of the project.

Professor Paul Johnson, Director of the Oxford Islet Transplant Programme and Professor of Paediatric Surgery at the University of Oxford, said: “Over the past 10 years, the transplantation of insulin-producing pancreatic cells known as islet cells (that can sense blood sugar levels and release insulin to maintain normal sugar levels) has achieved very promising results in adults who have developed the severest complications from insulin-dependent diabetes. The challenge is to now make sure that more people can benefit from this minimally-invasive treatment. Ultimately we would hope that it can be used to reverse diabetes in children soon after diagnosis. The DRIVE Consortium brings together some of the leading researchers in Europe in the fields of bioengineering, cell biology, and cell transplantation. The overall aim is to develop novel membranes to protect the transplanted islets from rejection ensure that islet transplantation can be undertaken without the need for the patient to take anti-rejection medication, with all the associated complications. This programme of research could be a real game-changer for people with Type 1 diabetes and the team in Oxford are very excited to be part of this state of the art research collaboration.”

The DRIVE Consortium represents a major interdisciplinary effort between stem cell biologists, experts in advanced drug delivery, research scientists, clinicians and research-active companies working together to develop novel therapeutics to address the challenges of treating diabtes. The researchers will optimise adult stem cell therapy using smart biomaterials and advanced drug delivery, and couple these therapeutics with minimally-invasive surgical devices.

Further Information about DRIVE

The project has recived funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 645991.

 Other partners include:

Royal College of Surgeon’s in Ireland (Ireland)

Dublin City University (Ireland)

Eberhard Karls University Tuebingen (Germany)

Utrecht University (The Netherlands)

University College Dublin (Ireland)

CIBER-BBN (Spain)

Abiel S.r.l. (Italy)

Contipro Pharma A.S.(Czech Republic)

Explora Biotech S.r.l. (Italy)

InnoCore Pharmaceuticals (The Netherlands)

Boston Scientific Ireland Ltd (Ireland)

INNOVA S.p.A. (Italy)

Ospedale Niguarda Ca’ Granda (Italy)

University of Oxford (UK)

Nanoencapsulated cells
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