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Posts Taged cancer-treatment

Stable nanovesicles for the delivery of microRNA in cancer treatment

  • Nanovesicles, known as quatsomes, have been successfully engineered to encapsulate and deliver microRNAs for the treatment of tumors.
  • These nanovesicles are produced by a simple GMP compliant process, an unavoidable requirement for the clinical use of new drug candidates.
  • The study, published in Small, has been highlighted in the Women in Materials Science issue of Advanced Materials.

“The beauty of these quatsomes nanovesicles is that they can be easily engineered for the delivery of a variety of nucleic acids. Importantly, they are stable at room temperature, which avoids problems associated to cold chain requirements, says Nora Ventosa, Scientific Director of NANBIOSIS U6.

MicroRNAs (also known as miRNAs) are small RNA molecules that can interfere with the stability of other RNA molecules (specifically, messenger RNA). They have many potential therapeutic uses due to the central role they play in major diseases. However, these molecules are still infrequently used in patients due to their instability in the bloodstream and their poor ability to reach specific tissues. A potential strategy to improve the clinical delivery of miRNAs in the body is to encapsulate them in tiny carriers that compensate its current shortcomings, without side effects and offering other complementary functions.

To this end, researchers have developed and designed especially for this application nanostructures, known as quatsomes, composed by two closed lipid layers. In a new publication in Small, which is highlighted in the “Women in Materials Science” Issue of Advanced Materials, researchers present a newly engineered formulation of quatsomes that have a controlled structure, composition and pH sensitiveness. 

The study is the result of an interdisciplinary team of researchers from the Institute of Materials Science of Barcelona, ICMAB-CSIC, the Vall d’Hebron Research Institute (VHIR)-UAB,  the Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Science and Technology (BIST),  the CIBER network on Bioengineering, Biomaterails and Nanomedicine (CIBER-BBN), the company Nanomol Technologies SL, the Technion-Israel Institute of Technology and the Institute for Complex Molecular Systems (ICMS).

“In this study we have collaborated with hospitals, research networks and companies. The successful results obtained illustrate the importance of collaboration across fields and beyond the academic system” says Ventosa.

These new quatsomes can be coupled with the miRNA and injected intravenously into the body to be delivered in neuroblastoma primary tumors or in frequent sites of metastasis, such as the liver or lung, with a higher success and stability than if the miRNA were injected by itself. Once delivered, the miRNA has an effect on the cell proliferation and survival-related gens in the tumors, decreasing the tumor’s growth rate.

Many properties make quatsomes a good fit for these applications: they are less than 150 nm in size and are stable in a liquid solution for more than 6 months; they also have tunable pH sensitiveness, which means that different pH levels around can trigger different responses.

Quatsome production and their physicochemical characterization has been performed by the ICTS “NANBIOSIS,” more specifically in the Biomaterial Processing and Nanostructuring Unit (U6), Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBER-BBN) located at the Institute of Materials Science of Barcelona (ICMAB-CSIC) and led by Nora Ventosa

The production of these nanovesicles has been optimized with their final application in mind and to make sure they can be used in clinics. Through a green and scalable one-step process, named DELOS, researchers have designed a procedure that is fully compliant with Good Manufacturing Practice (GMP) guidelines stablished by the European Union. “It is time to translate our scientific findings for the benefit of patients” says Ariadna Boloix, VHIR researcher.

The development of miRNA delivery systems containing an active targeting for neuroblastoma is performed under the frame of a CIBER-BBN valorization project “Targeted Quatsome nanocarriers for the delivery of microRNA for neuroblastoma therapy” (TAG-SMARTLY), coordinated by the Nanomol group in collaboration with the Multivalent Systems for Nanomedicine (MS4N) group of the CIBER-BBN at IQAC-CSIC and the Synthesis of Peptides Unit of Nanbiosis (U3).

In this publication, the functionality of quatsomes in delivering miRNAs is demonstrated with a specific extracranial solid tumor common in pediatric cases of cancer known as neuroblastoma, which is responsible for roughly 15 % of all pediatric cancer deaths and lacks therapies for high-risk patients. The results show that quatsomes protect the miRNA from degradation and increase its presence on liver, lung and xenografted neuroblastoma tumors, amongst other tissues.

Reference article:

Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics Ariadna Boloix, Natalia Feiner-Gracia, Mariana Köber, Javier Repetto, Rosa Pascarella, Aroa Soriano, Marc Masanas, Nathaly Segovia, Guillem Vargas-Nadal, Josep Merlo-Mas, Dganit Danino, Inbal Abutbul-Ionita, Laia Foradada, Josep Roma, Alba Córdoba, Santi Sala, Josep Sánchez de Toledo, Soledad Gallego, Jaume Veciana, Lorenzo Albertazzi, Miguel F. Segura*, Nora Ventosa* Small, 18, 3, 2022 DOI: 10.1002/smll.202101959

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

Nanoligent obtains the first prize in the Tech Transfer Competition in the ONCO Emergence forum

Nanoligent, the spin off created by the Directors of Units 1 and 18 of NANBIOSIS, awarded for the best company in Health Sciences given by the law firm RCD

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A new compound removes senescent cells and reduces toxicity in cancer treatment

  • Scientists of NANBIOSIS unit 26 NMR: Biomedical Applications II, (of CIBER-BBN and the Universitat Politècnica de València), together with researchers from the Principe Felipe Research Center and the University of Cambridge confirm the therapeutic potential of using a new conjugated drug, Nav-Gal, in combination with chemotherapy

  • Nav-Gal selectively removes tumourigenic senescent cells without attacking healthy cells and reduces the toxicity of platelets

The accumulation of senescent cells plays a significant role in cancer pathogenesis and other diseases. However, senolytic drugs (intended to remove senescent cells) present significant toxicity, which limits their therapeutic benefits.

Now, a new international study involving researchers at CIBER-BBN, the Universitat Politècnica de València (UPV) and the Principe Felipe Research Center, in collaboration with the University of Cambridge, have just proved the efficiency of a new conjugated drug, Nav-Gal, which selectively removes senescent cells, minimising the effect on healthy cells and reducing toxicity through this therapy. The use of this drug in combination with chemotherapy could be confirmed as a promising strategy in treating cancer. The auspicious results of this study have been published in the journal Aging Cell.

Senescent cells: the target

Senescence is a response to cell damage and stress characterised by the arrest of the cell cycle. When aging, cells permanently stop dividing, thus preventing the propagation of damaged and dysfunctional cells. However, eventually, a massive quantity of senescent cells accumulate in tissues, resulting in the onset and progression of multiple disorders, including diabetes, cardiovascular diseases, lung fibrosis, neurological disorders or cancer. Moreover, in the case of cancer, several chemotherapies result in cell senescence, and this accumulation of senescent cells due to the treatments has been related to tumourigenesis, associated with metastasis and the recurrence of tumours in different types of cancer. That is why the search for new drugs that remove senescent cells induced by cancer treatments is a key question in order to guarantee the total eradication of the tumour and prevent them from recurring.

On this front, senolytic drugs (compounds that kill senescent cells using several mechanisms) are a promising therapeutic alternative in oncology and for treating other diseases related to the accumulation of senescent cells. However, today senolytics present a low specificity because they also damage healthy cells, and have significant toxicities, which reduce their therapeutic benefits.

Reducing toxicity and preventing “collateral damages”

In this new study, published in Aging Cell, researchers at CIBER-BBN, the Universitat Politècnica de València (UPV) and the Principe Felipe Research Center, in collaboration with researchers from CRUK, at the University of Cambridge, worked on the design of a second-generation senolytic, which is more specific and less toxic. They focused on Navitoclax, a drug validated in preclinical models that proved to have a high capacity to destroy senescent cells, modifying it with acetylated-galactose.

The new compound, called Nav-Gal, results in a drug with selective, wide-ranging senolytic activity, which induces the death of senescent cells while preserving the activity of healthy cells.

“To summarize, we suggest the galactose conjugation with certain drugs as a versatile methodology to develop second-generation prodrugs with high senolytic activity and reduced toxicity,” explains Ramón Martínez Máñez, member of the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM) of the Universitat Politècnica de València, Scientific Director of CIBER-BBN and one of the study’s coordinators.

The researchers tested this drug in combination with chemotherapy (cisplatin) in human lung cancer cells, proving that treatment with cisplatin and Nav-Gal results in the eradication of senescent lung cancer cells and significantly reducing tumour growth. “This study provides evidence of the potential clinical application of combining senescence-induction chemotherapies with senotherapies in cancer,” explains Daniel Muñoz Espín from the CRUK Early Detection Programme of the University of Cambridge. Moreover, the compound Nav-Gal reduced platelet toxicity and the thrombopenia (reduction of the platelet circulation in bloodstream) caused by the previous drug, Navitoclax.

Reference article:

Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity



CIBER (Consorcio Centro de Investigación Biomédica en Red, M.P.) belongs to the Institute of Health Carlos III of the Spanish Ministry of Science and Innovation, and it is also funded by the European Regional Development Fund (ERDF). The CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) is made up of 46 research groups, selected for their renowned international scientific prestige, that mainly work within three scientific programmes: Bioengineering and Biomedical Imaging, Biomaterials and Tissue Engineering, and Nanomedicine. Its research work is oriented toward the development of prevention, diagnosis and monitoring systems as well as technologies for specific therapies such as Regenerative Medicine and Nanotherapies.

Further information

CIBER Communication Department

comunicacion@ciberisciii.es / 91 171 8119

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NANBIOSIS research to fight cancer

Twenty years ago, the 4 February was declared World Cancer Day with the global challenge of cancer would not be forgotten. Since then, huge progress has been made to understand, prevent, diagnose, and treat cancer.

NANBIOSIS as an ICTS (Singular Scientific and Technical infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples of the work carried out during the last year, are bellow:

Unit 20 of NANBIOSIS  at VHIR, works in several proyects reletaed to cancer as  H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells.

The activities of U1 of Protein Production Platform (PPP) are also strongly committed with several projects devoted to develop new, more selective and more efficient antitumoral drugs, with antimetastatic effects.
oordinated action between units U1 of Protein Production Platform (PPP),
U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, shows promising results in development of nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit  is also working on a joined initiative between CIBER-BBN and CIBER-ONC to improve the current ex vivo immune cell expansion systems to help introduce immunotherapies such as the adoptive cell therapies, which have shown complete remissions of terminal cancer patients, to the clinics overcoming the limitation of having enough therapeutic cells with novel Nanobiomaterials. Researchers of Unit 6 and researchers of Laboratory of Translational Research in Child and Adolescent Cancer from the Vall d’Hebron Research Institute (VHIR), are working on a project financed by the Spanish Government and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

In our unit U26. NMR: Biomedical Applications II,  several studies for cancer biomarker discovery are being carried out. NMR studies on biofluids for the design of novel strategies for diagnosis support, easily transferable into the clinical practice, are being developed in biofluids in the context of cancer. Urine is one of the most easily obtainable biofluid and is a non-invasive source of biomarkers. Among these studies, we can mention the good discrimination achieved between urine from bladder cancer patients before surgery (cancer) and urine after surgery (free of cancer) and in the follow up of the disease, to monitor relapses

Some of the results of these researchs have been published in scientific magazines of high impact as for exemple;

Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer Alba Loras, Cristian Suárez-Cabrera, M. Carmen Martínez-Bisbal, Guillermo Quintás , Jesús M. Paramio, Ramón Martínez-Máñez,
Salvador Gil and José Luis Ruiz-Cerdá. Cancers 2019, 11, 686; doi:10.3390/cancers11050686

Nanostructured toxins for the selective destruction of drug-resistant human CXCR4+ colorectal cancer stem cells Naroa Serna, Patricia Álamo, Prashanthi Rameshef, Daria Vinokurovaef, LauraSánchez-García, Ugutz Unzueta, Alberto Gallardo, María  Virtudes Céspedes, Esther Vázquez, Antonio Villaverde, Ramón Mangues, Jan Paul Medema. . Journal of Controlled Release.  Volume 320, 96-104, 2020 https://doi.org/10.1016/j.jconrel.2020.01.019

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering Voltà-Durán, E., Cano-Garrido, O., Serna, N. et al. CSci. China Mater.63, 147–156 (2020). https://doi.org/10.1007/s40843-019-9582-9

Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci, María Virtudes Céspedes  Olivia Cano‐Garrido  Patricia Álamo  Rita Sala  Alberto Gallardo  Naroa Serna  Aïda Falgàs  Eric Voltà‐Durán  Isolda Casanova  Alejandro Sánchez‐Chardi  Hèctor López‐Laguna  Laura Sánchez‐García  Julieta M. Sánchez  Ugutz Unzueta  Esther Vázquez  Ramón Mangues  Antonio Villaverde . Advanced Materiasls Número de artículo: 1907348 , Dec. 2019 https://doi.org/10.1002/adma.201907348

Artificial Inclusion Bodies for Clinical Development Julieta M. Sánchez  Hèctor López‐Laguna  Patricia Álamo  Naroa Serna  Alejandro Sánchez‐Chardi  Verónica Nolan  Olivia Cano‐Garrido  Isolda Casanova  Ugutz Unzueta  Esther Vazquez  Ramon Mangues  Antonio Villaverde, Advanced Science. 2019 https://doi.org/10.1002/advs.201902420

Nanostructured Nucleolin-Binding Peptide for Intracellular Drug Delivery in Triple-Negative Breast Cancer Stem Cells Mireia Pesarrodona, Laura Sánchez-García, Joaquin Seras-Franzoso, Alejandro Sánchez-Chardi, Ricardo Baltá-Foix, Patricia Cámara-Sánchez, Petra Gener,  José Juan Jara, Daniel Pulido, Naroa Serna, Simó Schwartz Jr. Miriam Royo, Antonio Villaverde, Ibane Abasolo, Esther Vazquez ACS Applied Materials & Interfaces DOI: 10.1021/acsami.9b15803  

Nanostructure Empowers Active Tumor Targeting in Ligand‐Based Molecular Delivery López‐Laguna, H., Sala, R., Sánchez, J. M., Álamo, P., Unzueta, U., Sánchez‐Chardi, A., Serna, N., Sánchez‐García, L., Voltà‐Durán, E., Mangues, R., Villaverde, A., Vázquez, E., . Part. Part. Syst. Charact. 2019, 36, 1900304. https://doi.org/10.1002/ppsc.201900304

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Release of targeted protein nanoparticles from functional bacterial amyloids: A death star-like approach

Sustained release of drug delivery systems (DDS) has the capacity to increase cancer treatment efficiency in terms of drug dosage reduction and subsequent decrease of deleterious side effects. In this regard, many biomaterials are being investigated but none offers morphometric and functional plasticity and versatility comparable to protein-based nanoparticles (pNPs). Researchers of NANBIOSIS units 1 and 18 are co-authors of an article  publish by Journal of Controlled Release in which it is described a new DDS by which pNPs are fabricated as bacterial inclusion bodies (IB), that can be easily isolated, subcutaneously injected and used as reservoirs for the sustained release of targeted pNPs. Our approach combines the high performance of pNP, regarding specific cell targeting and biodistribution with the IB supramolecular organization, stability and cost effectiveness. This renders a platform able to provide a sustained source of CXCR4-targeted pNPs that selectively accumulate in tumor cells in a CXCR4+ colorectal cancer xenograft model. In addition, the proposed system could be potentially adapted to any other protein construct offering a plethora of possible new therapeutic applications in nanomedicine.

In the study the researchers have generated novel smart biomaterials gathering most of the desirable features for implantable DDS, with cost effectiveness and simplicity in the biofabrication process. In this regard, single step fabricated IBs when injected subcutaneously rendered a long lasting release of targeted pNPs, able to enter to the blood stream and specifically target the tumor for as long as 10 days and they have described for the first time an approach for the fabrication of protein DDS based on protein deposition as IBs and their sustained release in form of fully functional targeted pNPs. This technology provides and stable source of targeted protein nanoparticles during long periods within the body with the action at distal points from the implantation site and pave the way for the appearance of new more efficient and less invasive treatments for a broad number of pathologies.

Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the U1. Protein Production Platform (PPP), whereas the in vivo biodistribution assays were performed in the NANBIOSIS U18. Nanotoxicology Unit,

For further information see https://sciencedirect.com/science/article/pii/S0168365918301780?via%3Dihub

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