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News U18

Protein-only Materials offer a new hope in colorectal cancer treatment

Breakthrough colorectal cancer treatment unveiled by NANBIOSIS Units promises enhanced precision & efficacy in targeted cancer therapies.

March 2024, UAB/Institut de Recerca Sant Pau/CIBER-BBN (Barcelona)

As we leave World Colorectal Cancer Day 2024 behind, marked on March 31st, there have been significant highlights in cancer treatment, a field in which targeted therapies are playing a crucial role.

In this context, researchers from the Nanobiotechnology team, at the Institut de Biotecnologia i de Biomedicina from Universitat Autònoma de Barcelona, led by Prof. Antonio Villaverde, in collaboration with the Oncogenesis and Antitumor Drugs team led by Prof. Ramón Mangues at Institut de Recerca Sant Pau, have made a significant breakthrough in the treatment of colorectal cancer. Their innovative approach, facilitated by their respective Unit 1 and Unit 18 of NANBIOSIS, promises to revolutionize current treatment methodologies and improve patient outcomes.

“In a clinical context, the use of these materials in the treatment of colorectal cancer should greatly improve the drug’s efficacy and patient comfort while minimizing unwanted side effects.”

Prof. Antonio Villaverde, Strategy Director of Unit 1

“It is important to highlight that such accumulation is more effective than when the protein is administered into the bloodstream. This fact offers a new and unexpected way to ensure high local levels of the drug and better clinical efficacy, avoiding repeated intravenous administration regimens,” explains Prof. Villaverde. “In a clinical context, the use of these materials in the treatment of colorectal cancer should greatly improve the drug’s efficacy and patient comfort while minimizing unwanted side effects.”

The team’s groundbreaking research centers around the development of self-contained protein-only materials at the microscale, capable of delivering therapeutic polypeptides in a time-prolonged manner. These materials, resembling the organization of secretory granules within the human endocrine system, are engineered to release functional polypeptide nanoparticles. These nanoparticles can selectively target tumors and destroy specific types of cancer cells, offering a promising avenue for more effective and precise cancer treatment.

The publication:

Notably, the researchers thorougly explored the molecular structure and dynamics of the secretion process of these materials, both in vitro and in vivo. In preclinical trials using an animal model of colorectal cancer, the system demonstrated remarkable efficacy upon subcutaneous administration. This was thanks to the released protein nanoparticles accumulating efficiently in tumor tissues. Importantly, this accumulation was found to be more effective than traditional intravenous administration methods, offering a novel strategy to ensure high local drug levels while minimizing systemic side effects.

A) Diagram illustrating theprotein administration protocol in a colorectal cancer mouse model. B) Accumulation of fluorescence in the tumour at days 1 and 10 after the administration, in two alternative formats (“IN” and “MPs”). Research product of a collaboration between NANBIOSIS Unit 1 and Unit 18. For more information, check the full publication at Adv. Sci. 2024, 2309427.

Furthermore, several competitive research and technology transfer projects supported this research, as well as intramural CIBER-BBN projects. This further highlights the importance of interdisciplinary collaboration and funding initiatives in driving scientific progress.

The team’s work underscores the importance of continued investment in research and collaboration to tackle the challenges posed by colorectal cancer and other malignancies. As World Colorectal Cancer Day is observed globally, this breakthrough offers hope for a future where innovative treatments pave the way for improved outcomes and enhanced quality of life for cancer patients worldwide.

The successful development of this innovative treatment approach was possible through the collaborative efforts of two NANBIOSIS Units: the Protein Production Platform (Unit 1) and the Nanotoxicology Unit (Unit 18).

References:

[1] J. M. Sánchez, H. López-Laguna, E. Parladé, A. D. Somma, A. L. Livieri, P. Álamo, R. Mangues, U. Unzueta, A. Villaverde, E. Vázquez, Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids. Adv. Sci. 2024, 2309427. https://doi.org/10.1002/advs.202309427

About NANBIOSIS:

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

In order to access our Cutting-Edge Biomedical Solutions, place your request here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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New immunization research for SARS-CoV-2 with the collaboration of NANBIOSIS

This novel immunization platform, recently published in ACS, triggers potent antivirus response, promising efficient and cost-effective vaccination.

March 2024, UAB/Vall d’Hebron Research Institute/CIBER-BBN (Barcelona)

The battle against infectious diseases demands innovative solutions. The world is especially aware of this fact after facing threats such as the SARS-CoV-2 pandemic. In a very recent publication in ACS Materials Letters, researchers from the Universitat Autònoma de Barcelona (UAB) and Hospital de Sant Pau, both within the CIBER-BBN, have achieved a significant milestone in vaccine development. Their study, conducted in partnership with international teams as well as NANBIOSIS, has introduced a novel immunization approach utilizing synthetic protein secretory granules.

These protein materials, developed by the team and highlighted in the study, exhibit endocrine-like functionalities tailored for the sustained release of protein drugs in oncology. At the microscale, these self-organized, self-contained protein granules undergo a spontaneous disintegration process associated with secretion, releasing their protein building blocks under physiological conditions. This technology, developed in collaboration with NANBIOSIS units, particularly the Protein Production Platform (Unit 1) and Nanotoxicology (Unit 18), holds promise beyond oncology, extending to various biomedical applications.

A promising solution to address not only existing infectious diseases but also future emerging threats.

The ACS publication:

In their work published last February 2024 [1], the researchers explored the potential of these synthetic protein secretory granules as an antigen delivery system for SARS-CoV-2. Thus, by utilizing a recombinant form of the virus’s receptor-binding domain, they investigated its efficacy in inducing neutralizing antibody responses in mice. Notably, the granules were administered without adjuvants, demonstrating their ability to trigger potent antivirus neutralizing responses.

Graphical abstract of the ACS Materials Letters paper, product of a collaboration with NANBIOSIS Unit 1 and Unit 18. ACS Materials Lett. 2024, 6, 3, 954-962.

The implications of this study are profound. Beyond the immediate context of COVID-19, this innovative immunization platform opens doors to more efficient vaccine delivery methods. By reducing dosage, costs, and the complexity of vaccination regimens, it presents a promising solution to address not only existing infectious diseases but also future emerging threats.

The collaborative nature of this research underscores the importance of synergistic partnerships. Alongside local institutions such as CIBER-BBN, ICREA, Institut de Recerca from Hospital Vall d’Hebró, and Hospital de Sant Pau, international collaboration with the University of São Paulo in Brazil has enriched the study’s scope and insights.

Funding for this groundbreaking research was provided by AGAUR through project 2020PANDE00003, and by CIBER-BBN through Intramural Projects NANOSARS and NANOREMOTE. Such support highlights the societal and scientific significance of this endeavor, emphasizing its potential to shape the future of vaccination strategies.

This publication marks a significant step forward in the fight against infectious diseases, showcasing the power of interdisciplinary collaboration and driving us towards a safer, healthier future. One in which NANBIOSIS will certainly contribute with the undisputable expertise of its researchers.

References:

[1] Zinc-Assisted Microscale Granules Made of the SARS-CoV-2 Spike Protein Trigger Neutralizing, Antivirus Antibody Responses. Marianna T. P. Favaro, Patricia Alamo, Nerea Roher, Miguel Chillon, Jara Lascorz, Merce Márquez, José Luis Corchero, Rosa Mendoza, Carlos Martínez-Torró, Neus Ferrer-Miralles, Luis C. S. Ferreira, Ramón Mangues, Esther Vázquez, Eloi Parladé, and Antonio Villaverde. ACS Materials Lett. 2024, 6, 3, 954–962. February 14, 2024 https://doi.org/10.1021/acsmaterialslett.3c01643

About NANBIOSIS:

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

In order to access our Cutting-Edge Biomedical Solutions, place your request here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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‘Magic Bullets’ Against Cancer: Unveiling the Potential of DNA Nanoparticles

DNA nanoparticles to selectively target tumor tissues through precise control of the synergies between transported drugs.

February 2024, IQAC-CSIC/CIBER-BBN, Barcelona. The team led by Drs. Carme Fàbrega and Ramón Eritja, in close collaboration with 3 units of the NANBIOSIS ICTS, has developed a new strategy to improve the efficacy and reduce the toxicity of anticancer drugs. They have chemically linked several cytotoxic drugs, currently used in the treatment of various types of tumors, to DNA nanostructures. These structures selectively target cancerous tissues through folate receptors. This tactic allows precise control of drug concentration and exploits their combined effect. The results of this study represent a significant step forward towards the development of more effective and safer cancer treatments. This year 2024, they published their study in the Nanomedicine journal by Elsevier.

“The ‘Magic Bullet’ of Dr. Ehrlich” is not the title of an old pulp magazine. Rather, it is the concept that the German physician and Nobel Prize winner coined to refer to an ideal therapeutic agent capable of acting specifically against a particular disease without affecting healthy cells.

In the case of cancer therapies, we are far from reaching that magic bullet. However, science is bringing us closer to it every day.

Many current anticancer drugs are designed to intercalate into the DNA of cells and alter their function, inducing cell death. One of the most significant problems with these therapies is their adverse effects, as these drugs can also affect non-tumor cells. One way to compensate for this is by combining multiple drugs, creating synergies between them. However, this often greatly hinders both drugs from reaching the target tissue at the appropriate concentrations to exert their synergy.

A strategy to approach the concept coined by the Nobel Prize involves selectively directing drugs towards cancerous tissues and releasing them in a controlled and localized manner. This increases their concentration in the tumor area, reducing the effect on the rest of the organs and tissues.

Thanks to the ability of many drugs to intercalate into DNA, one of the most promising vehicles are DNA nanostructures. These artificially constructed nanocarriers can retain the drug and, due to their enormous versatility, can be designed to selectively target the tumor. Once there, they release the drug in a controlled manner into the cancer cells, ensuring that healthy tissues are not exposed to a toxic concentration of the drug.

However, these DNA nanocarriers face several challenges: low internalization in diseased cells, low selectivity of the target tissues, or limited control over the amount of drug loaded inside and how it binds. Additionally, they only allow the transport of DNA intercalating drugs, limiting the range of applicable therapies.

In a recent study published in the Nanomedicine journal by Elsevier, the team led by Dr. Carme Fàbrega and Dr. Ramón Eritja, in close collaboration with 3 units of the NANBIOSIS ICTS, present a new approach [1]. Through a strategy to control the binding of the drug and its concentration within their DNA nanostructures, they have succeeded in increasing efficacy and reducing toxicity.

Instead of intercalating the drugs as usual, the researchers chemically conjugated each drug to a piece of the puzzle that would later form the nanostructure. They managed this way to precisely attach three anticancer drugs to their vehicles, each of them acting on a different anticancer mechanism and promoting a synergistic effect between them. Additionally, they achieved selective targeting by binding their nanostructures to folate receptors, expressed massively in a wide variety of tumor types.

This pioneering methodology is capable of attaching multiple drugs to DNA nanostructures, each at predetermined concentrations. This represents a leap forward in advancing towards the generation of that effective and harmless magic bullet that Dr. Ehrlich envisioned.

References

[1] Natalia Navarro, Anna Aviñó, Òscar Domènech, Jordi H. Borrell, Ramon Eritja, Carme Fàbrega, Defined covalent attachment of three cancer drugs to DNA origami increases cytotoxicity at nanomolar concentration, Nanomedicine: Nanotechnology, Biology and Medicine, Volume 55, 2024, 102722, ISSN 1549-9634, DOI: 10.1016/j.nano.2023.102722.

Additional information

In this project, three NANBIOSIS units have collaborated: Unit 12, with a characterization and scientific advisory role; Unit 18, providing one of the nanotoxic drugs; and Unit 29, contributing to the synthesis of oligonucleotides.

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates, along with their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

In order to access our biomedical Solutions, apply here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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Good News! Protein Nanoparticles with a New Ligand Select and Destroy Tumor-associated Fibroblasts”

With the participation of two units of NANBIOSIS ICTS and the expertise of the scientists managing these units

The study, fruit of the collaboration between the Nanotechnology group of the Institute of Biotechnology and Biomedicine (IBB-UAB), led by Prof. Antonio Villaverde, and the Oncogenesis and Antitumor Drugs group of the Sant Pau Research Institute, led by Dr. Ramon Mangues, both members of CIBER-BBN, has made significant progress by identifying the natural ligand PDGFD as an effective tool to target protein nanoparticles to tumor-associated fibroblasts that overexpress the PDGFR-β receptor. Given the relevance of the discovery, this technology has been intellectually protected by a patent that is currently being processed (PCT/EP2023/081937).

The research, the details of which have recently been published in the journal Acta Biomaterialia, presents an innovative strategy focused on the development of protein nanoparticles that assemble autonomously and are capable of selectively recognizing and destroying tumor-associated fibroblasts with high levels of PDGFR-β. This cell type plays a fundamental role in the tumor microenvironment, providing mechanical and biological support for tumor growth and progression in various types of cancers.

Taking advantage of their solid experience in the development of tumor-targeting protein nanoparticles and their functional characterization in in vitro and in vivo models of different types of cancer, both groups set out on this occasion to design new nanoparticles targeting tumor-associated fibroblasts with PDGFR-β overexpression. Among the different ligands tested, PDGFD has been selected for its ability to induce selective penetration into target cells both in vitro and in vivo, using a murine model with a subcutaneous tumor. In these experiments, the PDGFD-GFP-H6 fusion protein, formed by the chosen ligand, the green fluorescent protein and a histidine tail with an important role in obtaining nanoparticles, accumulates precisely in tumor tissues, demonstrating its ability from being delivered in tumor.

By replacing GFP with a microbial toxin present in antitumor treatments approved for clinical use, a significant reduction in tumor volume growth is observed, without showing toxic collateral effects in mice. In this way, the PDGFR-β/PDGFD couple has been validated as a versatile tool for the targeted delivery of drugs to the tumor microenvironment. These promising results pave the way for future developments in nanomedicine and offer new hope in the search for more effective and less invasive treatments for cancer patients.

The research has been performed with the collaborative participation of two units of the ICTS “NANBIOSIS”, more specifically the units U1 of Protein Production Platform, PPP and U18, Nanotoxicology Unit, and is framed in the context of the intramural collaboration of the CIBER-BBN “FIBOLISM”, coordinated by Dr Lorena Alba Castellon.

Referenced article

Eric Voltà-Durán•, Lorena Alba-Castellón• , Naroa Serna, Isolda Casanova, Hèctor López-Laguna, Alberto Gallardo, Alejandro Sánchez-Chardi, Antonio Villaverde, Ugutz Unzueta, Esther Vázquez, Ramón Mangues*. High-precision targeting and destruction of cancer-associated PDGFR-β+ stromal fibroblasts through self-assembling, protein-only nanoparticles. Acta Biomaterialia 170 543-555 (2023) https://doi.org/10.1016/j.actbio.2023.09.001

• Equal contribution

*Corresponding authors

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Impactful research with NANBIOSIS participation in the Poster Tour of CIBER-BBN & CIBEREHD Annual Conference.

2023 CIBER-BBN Annual meeting has taken place at Santemar Hotel, in Santander during November 6-7. This year the format of our annual conferences has been changed towards a collective event scheme between the CIBER-BBN and CIBEREHD thematic areas.

  • On Monday 6 the scientific sessions werecommon for EHD and BBN, with appealing contents for the mixed audience.
  • On Tuesday 7 EHD and BBN sessions will specific for each area in separate rooms (with common coffee break).

Posters of both areas were on display in the exhibit hall throughout the entirety of the Annual Meeting.

Moreover, at the “Posters & beers” session (Monday 6th: 6:00 p.m. – 7:00 p.m.) poster tours were organized where attendees could cast their vote for the best poster and use this one-on-one time with presenters to learn more, ask juicy questions and discuss their work. At 8:00 p.m., the awards ceremony took place for the best oral communication and best poster by young authors – for each area.

It was an impactful information sessions on research carried out by the groups of CIBER-BBN and CIBEREHD thematic areas.

The poster session is always a popular feature at CIBER-BBN Annual Meeting for acknowledgment NANBIOSIS units’ participation in the research carried out during the year. These are the works presented in 2023:

Targeted nanotoxin for the selective depletion of CXCR4+ cancer cells and immune cell recruitment in a colorectal cancer mouse model. Luis Miguel Carrasco-Díaz, Naroa Serna, Eric Voltà-Durán, Ugutz Unzueta, Esther Vázquez, Antonio Villaverde, Patricia Álamo, Lorena Alba-Castellón, Ramón Mangues. With participation of NANBIOSIS Units U1 Protein Production Platform (PPP) and U18 Nanotoxicology Unit . (Contact:
luismiguelcarrascodiaz@gmail.com)

Improvement of the biodistribution of GLA enzyme by RGD-functionalized nanoGLA in a Fabry mouse model.
Zamira Vanessa Diaz Riascos, Marc Moltó Abad, Daniel Marijuan, Belen García Prats, Judit Tomsen Melero, Elisabet González Mira, Jose Luis Corchero, Andreu Soldevila, Miriam Royo, Alba Córdoba, Nora Ventosa, Guillem Pintos Morell, Simo Schwartz , Ibane Abasolo. With participation of the NANBIOSIS units U20 FVPR-In Vivo Experimental Platform, U3 Synthesis of Peptides Unit and U6 Biomaterial Processing and Nanostructuring Unit. (Contact:
vanessa.diaz@vhir.org)

An auristatin-based nanoconjugate induces apoptosis and inhibits the bone marrow leukemia burden in an acute myeloid leukemia mouse model. Annabel Garcia-León, Julián I. Mendoza, Ariana Rueda, Luis Carlos Navas, Vanessa Huaca, Ugutz Unzueta, Jorge Sierra, Esther Vázquez, Antonio Villaverde, Ramon Mangues, Isolda Casanova. With participation of NANBIOSIS Units U1 Protein Production Platform (PPP) and U18 Nanotoxicology Unit. (Contact: agarciale@santpau.cat)

FVPR/U20-NANBIOSIS Service Platform: from the Synthesis and Characterization of Nanotechnology-based Therapies, to the in vitro and in vivo Preclinical Validation. Diana Rafael, Zamira V. Diaz Riascos, Belén García, Alejandra Palacios, Sandra Mancilla, Laura Garcia, Ibane Abasolo. Description of NANBIOSIS Unit 20 FVPR-In Vivo Experimental Platform. (Contact: diana.fernandes_de_so@vhir.org)

Non-Viral Vector Development for Gene Therapy in the Treatment of Congenital Liver Metabolic Diseases Lucía Enríquez Rodríguez, Isabel Carbonell Simón, Idoia Gallego Garrido, Virginia Nieto Romero, Iván Maldonado Pérez, Aida Garcia Torralba, Gustavo Puras Ochoa, Miruna Giurgiu, Jose Carlos Segovia Sanz, María García Bravo, Oscar Quintana Bustamante, José Luis Pedraz Muñoz. With participation of NANBIOSIS U10 Drug Formulation unit. (Contact: lucia.enriquez@ehu.eus)

X-ray Photoelectron Spectroscopy (XPS) Analysis of Nitrogen Environment in Small Extracellular Vesicle Membranes: A Potential Novel Technique with Application for Cancer Screening.
Ana Martín-Pardillos, María Sancho-Albero , Silvia Irusta , Víctor Sebastián , Vicente Luis Cebolla , Roberto Pazo-Cid , Pilar Martín-Duque , Jesús Santamaría. With participation of NANBIOSIS U9 Synthesis of Nanoparticles Unit. (Contact: a.martin_pardillos@unizar.es)

Nanoparticle-based approach for blood-brain-barrier crossing and glioblastoma treatment. Júlia German-Cortés, Raquel Herrero, Diana Rafael, Ibane Abasolo, Fernanda Andrade. With participation of NANBIOSIS Unit 20 FVPR-In Vivo Experimental Platform. (Contact: fernanda.silva@vhir.org)

Exploiting mammalian cells for recombinant protein production: an improved protocol for transient gene expression. Aida Carreño Fibla, Roger Fernández Palomeras, José Luis Barra, Rosa Mendoza Moreno, Mercedes Márquez Martínez, Neus Ferrer-Miralles, Antonio Villaverde Corrales, José Luis Corchero Nieto. With participation of NANBIOSIS Units U1 Protein Production Platform (PPP). (Contact:jlcorchero@ciber-bbn.es)

Surface characterization of a PLA/Qr/Mg biocomposite after in vitro degradation in m-SBF. Juan Manuel Casares-López, Margarita Hierro-Oliva, Verónica Luque-Agudo, Amparo M. Gallardo-Moreno, María Luisa González-Martín. With participation of Unit 16 Surface Characterization and Calorimetry Unit (Contact: mlglez@unex.es)

The poster session was an effective forum for the exchange of information and a means to communicate ideas

Related news:

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Nanoligent raised €2.8 M and completed Seed round financing with support of i&i Biotech Fund

September 27th 2022 – Nanoligent SL, a Spanish biotech company specialized in the development of cancer treatments based on unique protein conjugates, today announces the completion of a Seed financing round of total € 2.8 M. The final closing of the Seed round consists of € 1 M investment by i&i Biotech Fund I (i&i Bio), an early-stage Life Science fund with teams in Luxemburg and Prague which is backed by the European Investment Fund. i&i Bio joined previous Nanoligent investors, Italian Angels for Growth, the largest network of business angels in Italy, and AVANTECA Partners, a Swiss privately held asset management firm.
Jaromir Zahrádka, Managing partner of i&i Bio, said: “Nanoligent is the fifth investment of our fund and it belongs to a group of targeted oncology therapies in our portfolio. We are excited by deep scientific background and uniqueness of the technology. The platform is developed by highly motivated, experienced, and fully engaged team of scientists and managers. Based on obtained scientific data, the project has a great potential to become an effective treatment for multiple metastatic-cancer types.”
Nanoligent is focused on the development of new drugs for the treatment of more than 20 different metastatic cancer types. The lead molecule is based on the targeted elimination of cancer cells overexpressing the CXCR4 receptor, a recognized biomarker for poor prognosis and therapy resistance. Nanoligent is developing a new proprietary nano-technological platform, with the potential to overcome current limitations of Antibody-Drug-Conjugates.
“Less than a third of newly diagnosed metastatic patients respond to current therapies, making metastasis one of the most pressing unsolved challenges in cancer. With the support of i&i Bio together with our existing investors, we secure our current milestone to provide the first drug candidate of our portfolio of metastasis-targeted therapies” said Montserrat Cano, CEO of Nanoligent.
 The seed round financing will allow Nanoligent to foster the development of multiple drug candidates and advance the pre-clinical development of its lead candidate in a variety of tumor types.
 “We are happy to welcome the i&i Biotech Fund I in Nanoligent. As in previous cases, we have been impressed by the depth of their scientific due diligence and the professionality of their management. They are going to be an important partner for Nanoligent and we are delighted to continue to co-invest with i&i Bio,” said Michele Marzola who, together with Alessandro Toniolo, are co-champions from IAG in this investment.
Two of the investors already joined the Nanoligent’s Board which includes: Michele Marzola (IAG), Michael Milos (Avanteca Partners), Manuel Rodríguez (Chairman) and Montserrat Cano (CEO).
“The i&i Biotech Fund I is the right partner for the further development of Nanoligent. They have shown in depth scientific knowledge as well as being well connected within the pharmaceutical network. We all together are looking forward to bringing Nanoligent’s development plan effectively to the next stages,” said Michael Milos from AVANTECA Partners.

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About Nanoligent
Nanoligent was founded in 2017 by co-founder and Chairman Manuel Rodriguez Mariscal, as a spin-off coming from more than 10 years of fruitful collaboration between the Nanobiotechnology group – NANBIOSIS U1 PPP at the Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, co-lead by full professor Antonio Villaverde and Principal Investigator Esther Vázquez, and the Oncogenesis and Antitumor Drug Group – NANBIOSIS U18 Nanotoxicology Unit at the Biomedical Research Institut Sant Pau of the Hospital de la Santa Creu i Sant Pau, headed by full professor Ramon Mangues, the three of them also co-founders of the company. Montserrat Cano joined the company in 2020, with more than 15 years of experience in pharma and biotech companies. The aim of the company is to develop a pioneering technological platform based on protein-drug nanoconjugates to target metastasis across several tumor types. www.nanoligent.com

About Italian Angels for Growth
IAG, founded in 2007, is a leader in the Italian seed venture capital: more than 270 protagonists of the entrepreneurial, financial and industrial world that invest time, skills and capital for the growth of innovative startups. Italian Angels for Growth, in more than ten years of activity, has analyzed more than 6,500 startups and its members have made over 100 investments, for a total of over 300 million euros invested by IAG members and co-investors. IAG business angels support innovative projects financially by investing their own capital, but at the same time, thanks to the mix of skills of the members, support the founders of the startups in the definition of the business model in all its aspects. www.italianangels.net

About AVANTECA Partners
AVANTECA Partners is a Swiss-based, privately held asset management company that invests in early-stage life science companies. www.avanteca.com

About i&i Bio
i&i Bio is a Luxembourg-based venture capital firm that invests in innovative European Life Sciences companies focused on drug discoveries, medical devices, diagnostics, and digital health. The Fund was created thanks to the cooperation of the biotech incubator i&i Prague and the European Investment Fund (see below). With over €45M under management, i&i Bio plans to invest in about 20 early-stage companies. i&i Bio is led by an experienced team of professionals with backgrounds in private equity, healthcare and venture capital supporting entrepreneurs on their journey to global success. Thanks to the close cooperation with the fund’s sponsor, the biotech academic incubator i&i Prague, i&i Bio is supporting and advancing transformative Central European technology companies. www.inibio.eu

About European Investment Fund 
i&i Bio is supported by an investment from the EIF, with the support of:

lnnovFin Equity, with the financial backing of the European Union under Horizon 2020 Financial Instruments and the European Fund for Strategic Investments (EFSI) set up under the Investment Plan for Europe. The purpose of EFSI is to help support financing and implementing productive investments in the European Union and to ensure increased access to financing; and
the Pan-European Guarantee Fund (EGF), implemented by the EIF with the financial support of the Participating Member States. The objective of EGF is to respond to the economic impact of the COVID-19 pandemic by ensuring that companies in the Participating Member States have sufficient short-term liquidity available to weather the crisis and are able to continue their growth and development in the medium to long-term.Nanoligent SL – B66970088

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Wide representation of NANBIOSIS research in NALS 2022 and best Oral Presentation to Eloi Parladé

During the last 27-29 April, the 3rd International Conference on Nanomaterials Applied to Life Sciences 2022 (NALS 2022) has taken place in the Excellence Campus of Universidad de Cantabria in Santander (Spain), organized by the University of Cantabria and Institute Valdecilla-IDIVAL.

NALS 2022 has been a multidisciplinary conference series sharing new results and ideas in the fields of biosensors, lab on a chip, drug delivery nanopharmacy. nanobiotechnology, intelligent nanomaterials, magnetic materials, nanotoxicity, antimicrobials, novel applications of 3d bioprinting and nanoimaging.

NANBIOSIS has been represented at this edition by members of several of its units, among them we must highlight the set of four oral communication presented by members of the Nanobiotechnology group-Unit 1 of NANBIOSIS “Protein Production Platform (PPP)”, from CIBER-BBN and IIB-UAB the talks were delivered by:

Eloi Parladé: “Development of ion-dependent microscale secretory granules for nanomedical applications

Carlos Martínez-Torró: “Design of a human GFP-like protein scaffold for targeted nanomedicines

Eric Voltá Durán: “Antitumoral nanoparticles with multiple activities, a close reality

Jan Atienza-Garriga: “Characterization of protein-only NPs containing amps and analysis of their protection with liposomes and micelles

They summarized a wide area of the team activities on the design of protein-based protein materials for clinical uses, produced by means of diverse types of cell factories. In particular, antimicrobial peptides, cytotoxic proteins with antitumoral targeting and drug-carrying scaffold proteins are engineered to confer self-assembling properties as either microparticles or nanoparticles, that can be further functionalized with chemical drugs through covalent binding. Microparticles are of special interest as they can be used as slow drug delivery systems for nanostructured drugs upon subcutaneous administration. Alternatively, nanoparticles can be also presented as embedded in liposomes or other micellar structures that stabilize them for enhanced performance.

Three NANBIOSIS units supported the presented research, which has been executed in a highly cooperative way: namely U1 (Protein Production Platform), led by Tony Villaverde U18 (Nanotoxicology), led by Ramón Mangues and U29 (Oligonucleotide Synthesis Platform), led by Ramón Eritja.

Among all the excellent contributions by the team, it is worthy to stress that the prize for the best Oral Presentation was granted to Dr Eloi Parladé.

Other talk by researchers from NANBIOSIS were “Antioxidant-loaded polymeric NPs prepared by nano-emulsion templating for the management of neurological diseases” by Santiago Grijalvo, from NANBIOSIS U12 and  “Exploiting GSH oxidation with nanocatalysts to promote cancer cell death” by Javier Bonet-Aletá from NANBIOSIS U9

On the other hand, Jesús Santamaría,  Scientific Director of NANBIOSIS U9 was a Keynote Speaker in the Conference with the talk: “A change of paradigm in cancer therapy? Using catalysts to make drugs inside the tumor, rather than trying systemic chemotherapy”

NALS 2022 has been an excellent conference, with presentations covering a wide range of topics in nanomaterials for health, and a great opportunity for our researchers, especially for young’s, to let know their collaborative work, as well as make new connections on common research interests, thanks to the good socializing opportunities afforded by the scheduling of the organization conference.

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Nanoligent, whoes founders are leaders of NANBIOSIS units, raises €1M in Series Seed financing

Barcelona, Spain – Milan, Italy, February 3rd, 2022 – Nanoligent SL, a biotech company specialized in the development of nanotechnology-based cancer treatments, today announces the completion of the first closing of a Seed financing round of €1M. The round has been led by members of Italian Angels for Growth, the largest network of business angels in Italy, through the investment vehicle Nanolinvest, and AVANTECA Partners, a Swiss privately held asset management firm, both specialized in supporting innovative early-stage life-science companies primarily in Europe. An equity campaign, is still ongoing on Doorway, an online investment platform, thus promising to provide additional funding for the company.

NANOLIGENTis spin off from the Universidad Autónoma de Barcelona and Research Institute of the Hospital de Sant Pau – IIB Sant Pau that was created by the Directors of NANBIOSIS Units U18. Nanotoxicology Unit, Ramón Mangues and U1. Protein Production Platform (PPP), Antoni Villaverde, together with Esther Vázquez and Manuel Rodriguez

Nanoligent, is focused on the development of new drugs for the treatment of more than 20 different metastatic cancer types. The lead molecule is based on the targeted elimination of cancer cells overexpressing the CXCR4 receptor, a recognized biomarker for poor prognosis and therapy resistance. Nanoligent is developing a new proprietary nano-technological platform, with the potential to overcome current limitations of Antibody-Drug-Conjugates. The CXCR4 is overexpressed in a significant number of patients of more than 20 different tumors.

The financing will allow Nanoligent to complete the pre-clinical development in a variety of tumor types and to move its lead candidate into pre-IND stage.

The investor syndicate will join the Nanoligent’s Board which will consist of: Michele Marzola (IAG), Michael Milos (Avanteca Partners), Manuel Rodríguez (Chairman) and Montserrat Cano (CEO).

“We started the evaluation of a possible investment in Nanoligent one year ago and since then we have received enthusiastic responses from Key Opinion Leaders and Industry Experts. It has been a real pleasure working with the team at Nanoligent; we are impressed by their scientific depth and professional responses. We are continuing our fundraise for this deal together with Doorway, a fintech investing platform”, said Michele Marzola who together with Alessandro Toniolo are co-champions from IAG in this investment.

“We are fascinated by the technological capabilities of the platform and the professionalism of the team. The whole process was an intense, productive and very professional exchange. We are looking forward to partner with the management of Nanoligent to develop this highly innovative platform, which has the potential to transform cancer therapy” said Michael Milos from AVANTECA Partners.

“It is our great pleasure to welcome Michele Marzola and Michael Milos, whose expertise and experience will be a valuable addition to the company to accomplish its ambitious development plans over the next 18 months” said Montserrat Cano, CEO of Nanoligent.

Doorway, at its turn, is very happy to continue fundraising with its qualified community for such an innovative technology that can achieve a significant impact in the treatment of many cancers, being Nanoligent a perfect example of Doorway’s vision of “business with an impact”.

About Nanoligent

Nanoligent was founded in 2017 by co-founder and Chairman Manuel Rodriguez Mariscal, as a spin-off coming from more than 10 years of fruitful collaboration between the Nanobiotechnology group at the Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, co-lead by full professor Antonio Villaverde and Principal Investigator Esther Vázquez, and the Oncogenesis and Antitumor Drug Group at the Biomedical Research Institut Sant Pau of the Hospital de la Santa Creu i Sant Pau, headed by full professor Ramon Mangues, the three of them also co-founders of the company. Montserrat Cano joined the company in 2020, with more than 15 years of experience in pharma and biotech companies. The aim of the company is to develop a pioneering technological platform based on protein-drug nanoconjugates to target metastasis across several tumor types.

 About Italian Angels for Growth

IAG, founded in 2007, is a leader in the Italian seed venture capital: more than 270 protagonists of the entrepreneurial, financial and industrial world that invest time, skills and capital for the growth of innovative startups. Italian Angels for Growth, in more than ten years of activity, has analyzed more than 6,500 startups and its members have made over 100 investments, for a total of over 300 million euros invested by IAG members and co-investors. IAG business angels support innovative projects financially by investing their own capital, but at the same time, thanks to the mix of skills of the members, support the founders of the startups in the definition of the business model in all its aspects.

 About AVANTECA Partners

AVANTECA Partners is a Swiss-based, privately held asset management company that invests in early-stage life science companies.

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Dr Ramón Mangues, new member of the Royal Academy of Pharmacy of Catalonia

Dr. Ramon Mangues, head of the Oncogenesis and Antitumor Group and Scientific Director of NANBIOSIS U18 Nanotoxicology Unit of CIBER-BBN at the Sant Pau Research Institute, has been recently elected as a new member of the Royal Academy of Pharmacy of Catalonia.

The celebration will take place on November 8 at 7 pm, at the headquarters of the RAFC, (Royal Academy of Pharmacy of Catalonia) which was the headquarters of the old Hospital de la Santa Cruz since the 15th century, located at Calle del Hospital, 56, in Barcelona.

During the event, Dr. Mangues will read his admission speech “Selective delivery of drugs to metastatic stem cells“, which can be followed by zoom and live on Youtube using the following links:

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Development of a protein-only drug delivery system for sustained release

The Nanotoxicology Unit of CIBER-BBN ICTS NANBIOSIS (u18-nanotoxicology-unit), led by Ramon Mangues at the Research Institute of the Hospital de Sant Pau and the NABIOSIS (nanbiosis.es)Protein Production Platform (u1-protein-production-platform-ppp) led by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, have participated in the development of a novel drug delivery system able to achieve sustained release of proteins with intrinsic antitumor activity. This delivery system consists on inclusion bacterial bodies formed by recombinant fusion proteins that precipitate while being expressed in bacteria, acquiring an amyloid structure, but remaining functional. Thus, these amyloids are able to release protein monomers that generate soluble nanoparticles that selectively internalize within target cancer cells because of the incorporation ion the protein nanoparticles of a specific ligand that interacts with a surface receptor expressed in target cancer cells.

On this basis, we have subcutaneously administered inclusion bodies containing cytotoxic nanoparticles that incorporate the Pseudomonas aeruginosa Exotoxin (PE24), to demonstrate their capacity of sustained release since they reach cancer tissues through the blood to selectively killing target colorectal (CRC) cancer cells. This cancer specific targeting occurs because the released protein is functionalized with the peptidic ligand T22 for the CXCR4 receptor (overexpress in CRC cells). In addition, we have evaluated their anticancer effect in the different localization where metastatic foci growth in a colorectal cancer (CRC) model. The administration, in these models of 500 micrograms of T22-PE24 amyloids, induces a potent inhibition of primary tumor growth and a dramatic reduction, both in number and size, of the metastases in lymph nodes, liver, lung and peritoneum, an effect that is achieved, in the absence of systemic toxicity.

One of the main applications of these functional amyloid structures could be their use by subcutaneously injectable drug depots that could release the active protein drug at sustained levels, during a long time (weeks or months). This may change the way that current protein-based drugs (e.g. antibodies targeting specific receptors) are administered, since this approach will allow to dosage the drug only once every 2-3 weeks or a month, avoiding the current intravenous injection schedule, which is 2-3 times a week. When applied to targeted drugs, as the one here described, which demonstrate high efficacy with low adverse effects, could establish a novel approach to treat cancer patients by visits of sanitary personnel at their home, avoiding the need of their hospitalization, which is required when receiving intravenous injections; and therefore, dramatically reducing the cost of patient treatment for the health system. 

Reference:

Céspedes MV, Cano-Garrido O, Álamo P, Sala R, Gallardo A, Serna N, Falgàs A, Voltà-Durán E, Casanova I, Sánchez-Chardi A, López-Laguna H, Sánchez-García L, Sánchez JM, Unzueta U, Vázquez E, Mangues R, Villaverde A. Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci. Advanced materials. 2020.  https://doi.org/10.1002/adma.201907348

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