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The NABIHEAL Project Pioneers Wound Healing with New Biomimetic Matrices

Nearly 40 scientists across 7 countries are pioneering this breakthrough in wound healing using a nobel and affordable bio-inspired, anti-bacterial matrix.

In addition to the vast consortium, the project also comprises 5 small and medium-sized enterprises (SMEs) and 9 academic institutions. These were convened last February at the University of Granada to share insights, progress, and strategies.

According to an article published by UGR at the beginning of this month, about 40 researchers involved in the project have attended a meeting to share results and progress.

The Horizon Europe project NABIHEAL, coordinated by the Biomedical Research Networking Center (CIBER) at the Institute of Materials Science in Barcelona (ICMAB, CSIC), has held a consortium meeting. The international consortium consists of 14 partners from 7 countries, including 5 small and medium-sized enterprises (SMEs) and 9 academic institutions. These partners have expertise in the development, evaluation, and commercialization of products for wound healing, nanotechnology, safety, and regulation.

Who are the NABIHEAL project partners?

There are three groups from CIBER-BBN participating within NABIHEAL: two groups correspond to Unit 6 and Unit 16 of NANBIOSIS. The former is the NANOMOL Group, and is lead by Nora Ventosa, the project coordinator of NABIHEAL. The later corresponds to our Surface Characterization Unit from UEx. The third CIBER-BBN group is the Photonics Engineering Group (GIF) from the University of Cantabria, with several of its leaders working at NABIHEAL.

In addition, researchers from the UGR’s Advanced Therapies: Differentiation, Regeneration, and Cancer group, as well as the Clinical and Translational Dermatology group, are participating as one of the partners in this consortium. Both belong to the ibs.GRANADA Biosanitary Research Institute and the UGR’s Modeling Nature: from nano to macro Excellence Unit.

Professor Juan Antonio Marchal Corrales leads the project at the UGR and is part of the project’s steering and executive committees. This project is developed at the Singular Laboratory of Biofabrication and 3D (bio)printing (BioFabi3D), located at the Biomedical Research Center (CIBM). In addition, UGR and ibs.GRANADA, in collaboration with the company Bioibérica, contribute their expertise in the biofabrication and 3D bio-printing of human skin models based on components of the matrix of each of the skin layers.

About the meeting at UGR:

The meeting, held on February 7th and 8th, was inaugurated by the project coordinator, Nora Ventosa, Scientific Director of Unit 6 of NANBIOSIS and researcher at a researcher at CIBER and ICMAB-CSIC, and by Enrique Herrera, the Vice-Rector for Research and Technology Transfer of the University of Granada.

The meeting was attended by 38 researchers from among the NABIHEAL partners. These included the Biomedical Research Networking Center (CIBER) at the Institute of Materials Science in Barcelona (ICMAB); the University of Extremadura and the University of Cantabria; the Spanish National Research Council (CSIC); Nanomol Technologies S.L. (NT); Bioiberica S.A.U (BIO); Histocell S.L (HCELL); Asphalion (ASPH); MyBiotech GmbH (MyB); Charité-Universitätsmedizin Berlin (CH) from Germany; the Institute for Medical Research and Occupational Health (IMI) from Croatia; the University of Aarhus (AU) from Denmark; the Technion-Israel Institute of Technology (IT) from Israel; BioNanoNet Forschungsgesellschaft mbH (BNN) from Austria, and the University of Maribor (UM) from Slovenia, as reported by the UGR.

About NABIHEAL project:

NABIHEAL, “Nanostructured Antimicrobial Biomaterials for Healing Complex Wounds,” is funded by the Horizon Europe Research and Innovation program. It has a total budget of nearly 5 million EUR for the next four years. The project addresses two unmet medical needs in the healing of complex wounds: firstly, affordable treatments for wound infections and prevention of complications during healing, and secondly, a strategy to optimize the composition and efficacy of drugs and dressings for wound healing.

Aim of the project:

Complex wounds affect the quality of life of more than 2% of the population in developed countries. Thus, it is a global health problem with a significant impact on healthcare economics. Moreover, complex wounds, including chronic wounds or major burns, are highly susceptible to microbial infection and biofilm formation, making them difficult to treat. In this regard, silver is a widely used metal in antimicrobial products for treating wound infections. However, silver-based products are expensive and have various drawbacks due to costs and environmental and safety concerns.

The NABIHEAL project will develop multifunctional biomaterials to address some of the unmet medical needs in wound management. This project will provide affordable treatments for wound infections or prevention of complications during all phases of wound healing.

In the short and medium term, NABIHEAL will develop —at least— two innovative multifunctional biomaterials for wound healing, using affordable manufacturing technologies based in the EU. In the long term, NABIHEAL could become an alternative to silver in wound dressing for wound healing.

You can read more about NABIHEAL project at the official webpage here.

Meeting of NABIHEAL project members at UGR in February 2024. Source: UGR.

Additional information

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 goes 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:

Read More

Women in NANBIOSIS part 2: Ana Martín, and her Multi-degree Journey

We ask Dr. Martín about her innovations in cancer treatment with nanoparticles, in the context of her collaborations with NANBIOSIS.

This is part of a series of interviews to several female researchers within the context of International Day of Women and Girls in Science 2024. For more interviews, visit our news section here.

February 2024, INMA-CSIC/CIBER-BBN, Zaragoza (Spain)

We are walking through the tall corridors that connect the numerous blocks of the large R&D Building, located near the Río Ebro Campus of Unizar. This building is a conglomerate of institutes, laboratories, and research groups. In its dead center, open to the outdoors, a Zen Garden welcomes us, like an oasis of peace in the midst of this whirlwind of information, advancements, and scientific progress.

We enter the meeting room. The lights are flooding a large dark table surrounded by chairs. After a few minutes, Ana arrives. We greet each other warmly. It has been a long time since we last saw each other, perhaps since college? With a nervous laugh, she confesses, “Having a microphone in front of you is quite intimidating…”. She laughs again.

I consider making a joke right after the first question, in an attempt to reassure her. But I quickly change my mind as soon as she starts talking. Her nerves have completely dissipated, and her words, once shaky, now fill the recording with a confidence I didn’t expect. The confidence of someone who carries behind them a career as varied as it is fascinating.

The interview begins.

Well, Ana, tell us a little about yourself.

“My name is Ana. I have a degree in Veterinary Medicine, a degree in Biochemistry, and a Ph.D. from the University of Zaragoza. Currently, I work in the NFP group. My chemist colleagues synthesize nanoparticles, and I use them for anti-cancer treatments.”

What motivated you to choose a career in science?

“Since I was little, I’ve always been very interested in natural sciences. I’ve always been intrigued by how biological systems work, and over time, I became interested in pathology, the cause of diseases, and their treatment. That’s why when I had to choose a career, I chose Veterinary Medicine and, later, Biochemistry.”

Could you share with us a bit about your research area and the projects you are currently working on?

“Since I started working in research, I have been involved in the field of biomedicine, but the areas have been progressively changing. My career began in the field of aging and vascular diseases. Later on, I applied this knowledge to cancer research, which is the field I am currently working in, using nanoparticles as an anti-tumor treatment.”

What nanoparticles do you use?

“We use nanoparticles that, through catalysis, consume glucose and produce toxic species, inducing cell death specifically in tumor cells. We have many types of nanoparticles, especially by combining different types of metals. We introduce them into extracellular vesicles, which have tropism towards tumors, significantly improving the treatment compared to free nanoparticles.”

And what types of cancer do you treat?

“We use different cell lines from lung cancer, colon cancer, cervical cancer, brain cancer… We aim to create a treatment that is not specific to one type of cancer but can be applicable to many types of tumors. And high glucose consumption is something that tumors have in common.”

What have been the greatest challenges you have faced as a woman in the field of research?

“I believe the most difficult challenge has been balancing a scientific career with personal life, specifically with motherhood. When you work as a scientific researcher, there is never a perfect time to have children. You know that your career will be put on hold for a while, and research never stops, so there is a constant fear of falling behind. But as a scientist and a mother, I think one should never give up on motherhood because of it. In the end, everything is achievable, and personal life should never be sacrificed for professional life.”

Have you experienced any gender bias or added difficulty in your scientific career? How have you addressed this situation?

“In my case, I have been fortunate and I don’t believe I have experienced any gender bias. However, I do know of cases involving female colleagues who have encountered it.”

“There are challenging moments during a scientific career (…), but in the end, persistence pays off.

—Dr. Ana Martín, collaborator scientist in Unit 9.

What advice would you give to young women considering pursuing a career in science?

“My advice would be to enjoy the work in research. We have to remember that it is one of the best jobs out there; we are doing something for society, to improve it, whether working in biomedicine or other areas like technology. There are challenging moments during a scientific career, times when it’s difficult (due to lack of funding, opportunities, etc.), but in the end, persistence pays off. And if for some reason it doesn’t work out, all the knowledge gained will still be very useful in other areas.”

And what advice would you give to those who are unsure?

“Well, if they’re not sure… before diving into a doctoral thesis, they should visit laboratories, see how things work here, and choose something they enjoy. Because you’re going to spend a lot of time working on it, and the environment you’re in is very important.”

How do you think gender stereotypes can be overcome in your research field?

“I don’t believe there are gender stereotypes. However, it is true that currently, positions of greater responsibility are often held by men. In my opinion, equal opportunities should be given to men and women, and the time taken by women for their careers due to motherhood should not be penalized. This way, we can finally break the ‘glass ceiling’, and young people can also have female role models.”

And what about being a mother?

“In other countries, I’ve seen people having children during their doctoral thesis, and that’s unthinkable here. I believe the measures taken so far are just a patch and don’t fully compensate.”

What do you consider your greatest achievement or contribution in your field of study?

“Personally, my greatest achievement was obtaining a project on breast cancer in which I was Principal Investigator. As for my greatest contribution, I couldn’t say for sure. I believe everything I have done has contributed a little bit to research on vascular calcification, aging, and cancer. Perhaps it may seem somewhat insignificant, but it could be very important in aiding future research.”

What support have you received throughout your career that has been particularly helpful?

“The support of my family and my partner has been indispensable throughout my career. I also appreciate the support of the Government of Aragon and the European Union for the funding I received during my predoctoral and postdoctoral stages.”

What changes would you like to see in the scientific world to promote gender equality?

“I would like to see women not have to postpone or give up their personal lives for their work. I believe that, with the support of institutions, anything is achievable, as is the case in other European countries.”

How do you think we can encourage more women and girls to participate in science?

“I truly believe that there are more women in science than men. The problem is that leadership positions are almost never held by women, perhaps because many women end up sacrificing their careers for their personal lives, and that shouldn’t happen. We should break the glass ceiling and allow women to access leadership positions so that girls have examples of female scientists to follow and don’t think that science is only for men.”

It’s been a pleasure to see you again and chat with you, Ana. And thank you for your time.

“Thanks to you too.”

For more interviews like this, visit our news section here.

Additional information:

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 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:

Read More

Women in NANBIOSIS part 1: Anna Aviñó, from Curiosity to Innovation

Anna Aviñó speaks about her journey as a researcher and her captivating oligonucleotides.

This is part of a series of interviews to several female researchers within the context of International Day of Women and Girls in Science 2024. For more interviews, visit our news section here.

February 2024, IQAC-CSIC/CIBER-BBN, Barcelona (Spain)

Could you share with us a bit about your research area and the projects you are currently working on?

I am a chemist specializing in nucleic acid chemistry. These compounds are wonderful, I would say unique; not only do they contain genetic information, but they are also involved in countless biological processes. My focus lies in synthetic and structural studies of small nucleic acids, known as oligonucleotides.

And these compounds, what are they used for?

Oligonucleotides can adopt different structures, including canonical duplexes as well as other secondary structures like quadruplexes and triplexes, the latter being particularly important in many diseases. I apply my chemical knowledge to generate and evaluate therapeutic oligonucleotides (such as antisense, siRNA, aptamers). Furthermore, oligonucleotides are so versatile that I also use them as recognition elements in various biosensors to detect pathogens, disease-related genes, etc.

“Oligonucleotides (…) are recently being approved as new advanced gene therapies for many diseases, including rare and cardiovascular diseases.

—Dr. Anna Aviñó, scientific coordinator of Unit 29.

What motivated you to choose a career as a researcher? What have been the biggest challenges you have faced as a woman scientist?

I wanted to understand what things are made of, how medicines are made… I am currently 55 years old with a long scientific career, but it has never been easy to balance top-level research with family life. I have to thank CIBER as it’s the longest contract I’ve had, but I also have to say that I haven’t had opportunities for career advancement within it.

Have you experienced any kind of gender bias or added difficulty in your scientific career? How have you addressed this situation?

I haven’t faced any added difficulty per se, but the reality is that in my research center, the principal investigators are predominantly women with few family responsibilities.

How do you think gender stereotypes in the scientific field can be overcome? And what advice would you give to young women considering a career in science?

I think that stereotypes can be overcome by promoting unbiased education in schools regardless of the field of study. I would definitely encourage young women and advise them not to be afraid to pursue positions of responsibility.

What do you consider to be your greatest achievement or contribution in your field?

The oligonucleotides, which are my area of study as I mentioned, are recently being approved as new advanced gene therapies for many diseases, including rare and cardiovascular diseases. I can say that I can synthesize drugs in my laboratory, and furthermore, I believe I am the person who has conducted the most synthesis of these products in Spain!

What support have you received throughout your career that has been particularly helpful?

As I mentioned, thanks to CIBER, I continue to be a researcher. However, I am currently in a delicate situation because my principal investigator is retiring, and I don’t know how my scientific career will continue.

What changes would you like to see in the scientific world to promote gender equality? How do you think we can encourage more women and girls to participate in science?

The scientific world is not particularly biased in terms of gender equality. However, leadership positions tend to be held by men, even though more women are starting careers in research. Regarding encouraging more women, as I mentioned, education. Education is the key.

For more interviews like this, visit our news section here.

Additional information:

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 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:

Read More

Polymeric Micelles Delivering Hope: A Revolutionary Strategy to Fight Cancer

NANBIOSIS researchers reach intracellular targets with encapsulated antibodies.

February 2024, IQAC-CSIC/CIBER-BBN, Barcelona (Spain) and Santiago (Chile)

Dr. Abasolo and her team have developed an innovative strategy to combat intracellular oncogenes, notably KRAS, implicated in various deadly cancers. By encapsulating therapeutic antibodies within polymeric micelles, they have successfully facilitated the entry of these antibodies into cancer cells, targeting internal markers. This breakthrough, achieved through international collaboration, represents a significant advancement in cancer treatment and holds promise for addressing other diseases with intracellular targets. These findings provide hope for improved therapies and outcomes in cancer and beyond.

Every individual is said to have an inner enemy, lurking to sabotage under favorable circumstances. In the case of our cells, this rings particularly true. Some genes are as necessary for their proper function as they are dangerous when they malfunction. Those that, under certain circumstances, promote tumor development are known as oncogenes. But we now have new tools to combat them.

In the ongoing battle against cancer, researchers have reached a significant milestone in combatting intracellular oncogenes. Thanks to a groundbreaking strategy developed by Dr. Abasolo and her team from Unit 20, they managed to reach particularly difficuly intracellular targets. Their innovative approach involves utilizing therapeutic antibodies encapsulated in polymeric micelles, facilitating their entry into cancer cells and targeting internal markers. The results, achieved through international collaboration, mark a significant advancement in cancer treatment and hold promising possibilities for addressing other diseases with intracellular targets.

KRAS is the name given to one of these oncogenes, and it’s a particularly dangerous foe. The small protein produced by the KRAS gene is a molecular switch that controls numerous cellular functions, including survival, proliferation, differentiation, and migration. When KRAS mutates, this switch stops working, preventing the cell from self-regulating, often leading to some of the most malignant and lethal types of cancer, such as pancreatic, colon, or lung cancer. Moreover, this mutated protein is difficult to target due to its unique molecular structure and the fact that it resides within the cell. However, thanks to our new anti-tumor technology, we’re able to reach it.

One method of blocking mutated KRAS is through the use of therapeutic antibodies. These antibodies, by specifically binding to the protein, inhibit its function, halting the malignancy of cancer cells. However, one of the challenges in using these antibodies is that they cannot enter cells on their own. None of the attempts to internalize them have been successful, until now.

In a recent study published last year, the team led by Dr. Abasolo, in which our Unit 20 is integrated, has successfully attacked mutated KRAS using anti-KRAS antibodies. To achieve this, they encapsulated the antibodies in nanometric drug delivery systems (NanoDDS). Specifically, they used micelles composed of a polymer capable of surrounding the antibodies, facilitating their entry into cells. Furthermore, these nanostructures enable passive and selective entry into tumors and, to top it off, the polymer used prevents the emergence of dreaded cancer multi-drug resistances.

These unprecedented results are the product of international collaboration, where in silico simulation, in vitro assays, and animal studies have gone hand in hand. These results have demonstrated the effectiveness of a new tool capable not only of serving in the fight against cancer, but also of acting on therapeutic intracellular targets present in many other diseases. A way to defeat that inner enemy.

References

[1] Diana Rafael, Sara Montero, Pilar Carcavilla, Fernanda Andrade, Júlia German-Cortés, Zamira V. Diaz-Riascos, Joaquin Seras-Franzoso, Monserrat Llaguno, Begoña Fernández, Alfredo Pereira, Esteban F. Duran-Lara, Simó Schwartz Jr., and Ibane Abasolo. Intracellular Delivery of Anti-Kirsten Rat Sarcoma Antibodies Mediated by Polymeric Micelles Exerts Strong In Vitro and In Vivo Anti-Tumorigenic Activity in Kirsten Rat Sarcoma-Mutated Cancers. ACS Applied Materials & Interfaces 2023 15 (8), 10398-10413 DOI: 10.1021/acsami.2c19897

Additional information

In this project, Unit 20 of the NANBIOSIS ICTS has collaborated, providing both functional validation and all preclinical trials with murine models. All of this has been conducted following the strictest ethical guidelines.

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 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:

Read More

Women in NANBIOSIS: Our New Interview Series

In celebration of the International Day of Women and Girls in Science 2024, NANBIOSIS proudly presents a series of insightful interviews featuring some of our most esteemed female researchers and collaborators.

As we commemorate this important day, join us in honoring the achievements of these remarkable individuals, as they share their perspectives, challenges, and triumphs in the pursuit of scientific excellence. Explore our news section for more inspiring interviews, and discover the diverse talents driving innovation within NANBIOSIS and beyond.

Drs. Anna Aviñó, Fany Peña, Ana Martín, María Sancho, Susana Vilchez, Ana Mincholé and, of course, Dr. Elisabeth Prats, all of them we had the pleasure and privilege to intervew and tell part of their story, career, projects, prospects and motivations. Delving into their remarkable contributions and experiences, this series sheds light on the invaluable role women play in shaping the field of biomedical research.

Starting tomorrow, February 12, and continuing until Women’s Day on March 8, immerse yourself in this captivating series, as we highlight the profound impact of female leadership in science and technology. Witness firsthand the passion, dedication, and ingenuity of these pioneering women, as they navigate the frontiers of biomedical research and innovation.

Join us in celebrating the women driving innovation and shaping the future of science. Visit our news section to dive into this captivating series and discover the transformative impact of female leadership in NANBIOSIS.

This is part of a series of interviews to several female researchers within the context of International Day of Women and Girls in Science 2024. For more interviews and updates, visit our news section here.

Additional information:

For those eager to explore further, NANBIOSIS offers comprehensive and integrated advanced solutions in biomedical applications, ranging from biomaterials to nanomaterials and their nanoconjugates. Partner with us to unlock cutting-edge biomedical solutions, designed to address diverse challenges in drug delivery, biomaterials, and regenerative medicine. Apply now to access our transformative biomedical solutions.

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 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:

Read More

Bringing Hope to Cancer Treatment: New Pioneering Advances in Nanotechnology

NANBIOSIS Researchers Lead the Way in Innovative Nanomedicine Approaches

Cancer remains a formidable challenge globally, with 19.1 million cases diagnosed in 2020, resulting in nearly 10 million deaths. However, amidst these alarming statistics, a beacon of hope emerges from the field of nanomedicine.

Spearheaded by Professor Jesus Santamaria and his team at the NFP group, part of the NANBIOSIS ICTS Unit 9, groundbreaking advancements in nanotechnology are revolutionizing cancer treatment. Funded by the European Research Council, their efforts mark a significant stride towards more effective and targeted therapies.

“The potential adverse effects (of antineoplastic agents) on healthy cells is the main limitation, in addition to the development of drug resistance by cancer cells.”

—Dr. Jose L. Hueso, Scientific Coordinator of Unit 9

Traditional cancer treatments like surgery, chemotherapy (CT), and radiotherapy (RT) have long been the mainstays of clinical intervention. While effective, their indiscriminate nature often leads to debilitating side effects and the development of dreaded drug resistances in cancer cells. Chemotherapy, in particular, poses significant challenges due to its adverse effects on healthy cells.

This is where nanoscience and nanotechnology come to play. These cutting-edge disciplines offer promising avenues for the development of selective and precise cancer therapies. The work of Prof. Santamaria’s team focuses on leveraging nanoparticles to deliver tailored treatments directly to cancerous tissues while minimizing collateral damage to healthy cells.

Their innovative approach involves the synthesis of inorganic and carbon-based nanoparticles with enzyme-mimicking capabilities. These nanoparticles exhibit a multifaceted response within the tumor microenvironment, from consuming glucose to generating reactive oxidative species. Moreover, they disrupt the antioxidant defense mechanisms of cancer cells, rendering them more susceptible to treatment.

Collaborative efforts with esteemed researchers like Pilar Martin Duque, Luisa de Cola, and Asier Unciti-Broceta further enhance the potential of these nanotherapeutic strategies. Together, they strive to refine nanoparticle delivery systems, protect the catalytic activity in the tumor microenvironment, and engineer anticancer prodrugs using bioorthogonal chemistry.

The implications of these advancements are profound. By harnessing the power of nanotechnology, researchers have the tools to revolutionize cancer treatments. With greater specificity and reduced toxicity, nanotherapies offer renewed hope for patients battling this relentless disease.

As the field of nanotechnology continues to evolve, the potential for personalized, precision medicine approaches tailored to individual patients becomes increasingly tangible. With the expertise of NANBIOSIS ICST researchers at the forefront of this revolution, the future of cancer treatment shines brighter than ever before.

NFP group: Members currently working on the development of novel strategies of synthesis, encapsulation and delivery of active catalysts against cancer include: Dr. Víctor Sebastián, Dr. Ana Martín, Dr. María Sancho, Dr. Jose L. Hueso, Dr. Javier Bonet and PhD students: Andrea Mosseri, Ángeles Valls, Miguel Encinas, Jose Ignacio Garcia Peiro, Leticia Sanchez, Estefanía Chico.

Additional information

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:

Read More

‘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:

Read More

1st Open call 2024 for preferential access to the ICTS NANBIOSIS

NANBIOSIS opens in February the 1st competitive open call 2024 for its “Cutting-Edge Biomedical Solutions” and services.

NANBIOSIS is a research infrastructure for Biomedicine in which three cutting-edge public institutions collaborate forming a deeply interconnected laboratory network: CIBER-BBN, CCMIJU and IBIMA-Plataforma BIONAND. In addition, NANBIOSIS is part of the Spanish Map of ICTS (Spanish for “Scientific and Technical Unique Infrastructures”), approved by the Spanish Ministerio de Ciencia, Innovación y Universidades .

Our publicly funded facilities and internationally renowned scientist will help you design and test biomedical solutions to your heart’s content. We are open to all interested national and international users who may come either from the public or the private sector. You can apply to use our services in two modalities: under the “Competitive Open Access” (within two designated calls) or by “Access on Demand”, your choice.

To make that happen, at least 20% of the NANBIOSIS Units’ capacity is granted on the Competitive Open Access modality. The proposals granted under this modality will be prioritized according to criteria of scientific and technical quality and singularity. In addition, a 5% discount will be applied for those proposals that resort to at least one of our integrated services, the Cutting-Edge Biomedical Solutions.

There are 2 calls per year for Competitive Open Access that allow the prioritization of the best proposals. Click here to apply.

The next call will open on February 1st. The applications can be submitted throughout the whole month (due date February 29th). Access application forms submitted after that date will be processed under the “Access on Demand” modality.

Proposals granted in the Competitive Open Access modality must meet, at least, one of the circumstances listed in the access application form (“order request“), in order to demonstrate their scientific and technical quality or singularity.

Thus, for example, applications related to R&D projects funded through national or European calls are eligible. In addition, the proposals are required to use one of the NANBIOSIS Cutting-Edge Biomedical Solutions”. That implies the interaction of at least two of our Units, which can be modified to your specific needs.

NANBIOSIS Cutting-edge Biomedical Solutions

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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NANBIOSIS U1_Protein Production Platform expands its facilities at the Autonomous University of Barcelona, strengthening its capabilities.

NANBIOSIS Unit 1 Protein Production Platform (PPP) of CIBER-BBN and UAB, has taken a significant step towards enhancing its service capabilities in the field of recombinant protein production and purification.

Until now, due to space constraints at the Institute of Biotechnology and Biomedicine (IBB), U1’s activities were confined to half of a small laboratory. However, thanks to the ongoing commitment of the center to bolster the PPP’s activities, this unit has gained access to a laboratory, along with an office, exclusively designated for the platform within the IBB premises, creating an optimal environment for the process of protein production and purification.

This initiative has not only solidified the space that PPP occupies within the IBB and the UAB but also signifies a boost for UAB’s internal services, reinforcing its position as an integral part of ICTS NANBIOSIS, thereby strengthening its commitment to research and scientific excellence.

The center, in its steadfast support for PPP’s activities, has prioritized the allocation of this new space over other needs, recognizing the potential and strategic importance of this service for advancing molecular research, not only within the institution but also within the scientific community at large.

The immediate impact of this facility expansion has resulted in the provision of an optimal space to accommodate all FPLC-AKTA purification equipment, essential for providing quality service. Additionally, new equipment has been acquired, notably including the incorporation of a large-sized refrigerator capable of housing a FPLC-AKTA unit. This development represents a qualitative leap, enabling the PPP to optimize processes for purifying thermosensitive proteins.

The new spaces of the PPP are now adjacent to the spaces of the Nanobiotechnology Group (NBT), enhancing the exchange of information and knowledge between both, and facilitating direct access to shared resources, thereby stimulating interaction. The combination of expertise in protein design and purification with specialization in nanobiotechnology opens up a broad horizon for innovation and the development of disruptive solutions in various fields.

In the words of the responsible team, “this expansion represents a significant step forward, allowing NANBIOSIS U1 not only to advance in its current service provision but also to open doors to new improvement opportunities”.

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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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