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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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Three articles acknoledging NANBIOSIS contribution awarded at the Bioaraba Research and Innovation Conference

Researchers of NANBIOSIS U10 “Drug Formulation” – NanoBiocel research group from CIBER-BBN and UPV/EHU receives 3 awards in the category of Best International Articles at the annual Bioaraba Research and Innovation Conference.

On 4 November, the Bioaraba Health Research Institute held its XXIII Research and Innovation Conference in Vitoria. This important annual forum held in the city brings together professionals from the health system of Alava, the Rioja region of Alava, the Mental Health Network of Alava, the University of the Basque Country and also professionals from companies in R&D&I in health.

On this occasion, the NanoBioCel research group of the CIBER BBN and the ICTS Nanbiosis through the U10 Drug Formulation, won the 3 prizes in the category of Research and Innovation in the category of Best International Article. The first prize went to the article: Mesenchymal stromal cells encapsulated in licensing hydrogels exert delocalized systemic protection against ulcerative colitis via subcutaneous xenotransplantation. Written by Ainhoa Gonzalez-Pujana, Ana Beloqui, José Javier Aguirre, Manoli Igartua, Edorta Santos-Vizcaino, Rosa Maria Hernandez, published in the European Journal of Pharmaceutics and Biopharmaceutics in 2022. The second prize went to the article Nanodiamond Integration into Niosomes as an Emerging and Efficient Gene Therapy Nanoplatform for Central Nervous System Diseases whose authors are: Nuseibah AL Qtaish, Idoia Gallego, Alejandro J. Paredes,Ilia Villate, Cristina Soto-Sánchez, Gema Martínez, Myriam Sainz-Ramos, Tania B. López, Eduardo Fernández, Gustavo Puras, José Luis Pedraz. And the third prize went to the review: Cell microencapsulation technologies for sustained drug delivery: Latest advancesin efficacy and biosafety whose authors are: Tania B. López, Edorta Santos, José Luis Pedraz, Gorka Orive, Rosa María Hernández.

Articles of refernce:

Ainhoa Gonzalez-Pujana, Ana Beloqui, José Javier Aguirre, Manoli Igartua, Edorta Santos-Vizcaino, Rosa Maria Hernandez, “Mesenchymal stromal cells encapsulated in licensing hydrogels exert delocalized systemic protection against ulcerative colitis via subcutaneous xenotransplantation“, European Journal of Pharmaceutics and Biopharmaceutics, Volume 172,
2022, https://doi.org/10.1016/j.ejpb.2022.01.007

Nuseibah AL Qtaish, Idoia Gallego, Alejandro J. Paredes, Ilia Villate-Beitia, Cristina Soto-Sánchez, Gema Martínez-Navarrete, Myriam Sainz-Ramos, Tania B. Lopez-Mendez, Eduardo Fernández, Gustavo Puras, José Luis Pedraz. “Nanodiamond Integration into Niosomes as an Emerging and Efficient Gene Therapy Nanoplatform for Central Nervous System DiseasesACS Appl. Mater. Interfaces 2022, 14, 11, 13665–13677 https://doi.org/10.1021/acsami.2c02182

Tania B. Lopez-Mendez, Edorta Santos-Vizcaino, Jose Luis Pedraz, Gorka Orive, Rosa Maria Hernandez, “Cell microencapsulation technologies for sustained drug delivery: Latest advances in efficacy and biosafety,
Journal of Controlled Release”,
Journal of Controlled Release, Volume 335, 10 July 2021, Pages 619-636 https://doi.org/10.1016/j.jconrel.2021.06.006


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1st Nanomedicine Forum of CIBER-BBN/NANBIOSIS and CSIC Nanomed Conection

During the days 30 of June and 1st of July took place in Barcelona, in the auditorium of the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), the 1st Forum on Nanomedicine gathering scientists from the CSIC net Nanomed Conection and from the CIBER-BBN and its ICTS NANBIOSIS.

This forum brought toguether researchers from the most eminent national research centers in nanomedicine, that during the two days meeting presented their works and findings and discussed the impact of nanomedicine in the fields of drug delivery, diagnosis and therapy.

The workshop was open by the Director of IQAC-CSIC,  Jesús Joglar, the  Scientific Coordinator of Nanomed Conection, Fernando Herranz, and the Scientific Director of CIBER-BBN, Ramón Martínez Máñez.

18 research groups gave their talks distributed in four sessions:

  • Nanobiotechnological solutions for diagnosis and therapy
  • Drug delivery nanosystems
  • Applications for oncology 
  • Nanomedicine & other frontier applications

The presentations aroused great interest and futher debate among the attendees present in the auditorium (around 50) and the on line participants (The event was also broadcast online previous registration with more than 125 registrations received).

The videos of the presentations will be soon available in the NANBIOSIS youtube channel.

Here we highlight the eight talks by researchers from NANBIOSIS units:

The first session of Nanobiotechnological solutions for diagnosis and therapy,  started  with the talk by Montserrat Rodríguez from Nb4D group NANBIOSIS U2 CAbS, from CIBER-BBN and IQAC-CSIC, entitled “Targeting aromatic amino acid metabolism for the early diagnosis of neurological diseases”, presenting their results on in vitro samples, on thermal power characterization experiments to study the thermal efficiency of non-sinusoidal stimulation and on efficiency characterization experiments in cell cultures with cancer cell liness.

Also in this session chaired by Miriam Royo, Scientific Coordinator of NANBIOSIS U3 Synthesis of Peptides Unit of  CIBER-BBN and IQAC-CSIC,  took place an interesting and passionate talk by Ramón Eritja, Scientific Director of NANBIOSIS U29 Oligonucleotide Synthesis Platform (OSP)

In the last years, interest in therapeutic applications of oligonucleotides has increased enormously, especially after the development of messenger RNA vaccines in response to the COVID-19 pandemic. In this way, metabolic diseases such as dyslipidemia and hereditary diseases such as Duchenne muscular dystrophy have been successfully addressed. The NANBIOSIS  Oligonucleotide Synthesis Platform (OSP) focuses on the design, synthesis and characterization of modified oligonucleotides, in order to enhance the therapeutic properties of the oligonucleotides and to improve the control of gene expression. Ramon Eritja presented their most recent results in the development of new conjugates with antiproliferative activity and in the design of DNA probes for the detection of viral genomes.

 

In the session of “Nanomedicine and other frontiers applications”, chaired by María del Puerto Morales Herrero (ICMM-CSIC), Elena Martínez Fraiz,  from the Nanobioengineering group of CIBER-BBN and IBEC running NANBIOSIS Unit 7 of Nanotechnology, presented  a nanostructured surface able to produce multivalent effects of surface-bound ephrinB1 ligands on the dynamics of oligomerization of EphB2 receptors  whic can benefit applications such as the design of new bioactive materials and drug-delivery systems.

The session of Drug delivery nanosystems, chaired by Ramón Martínez Máñez, began with the talk by Vanessa Díaz Riascos, presesnting the in vivo efficacy, biodistribution and toxicity testing of nanomedicines at NANBIOSIS U20 FVPR, of CIBER-BBN and VHIR, explaining how their texting expertise and their in vivo and ex vivo fluorescence imaging techniques facilitate a rapid and efficient preclinical development of candidates, reducing considerably the time and costs of conventional developments.


Santiago Grijalvo Torrijo, from NANBIOSIS U12 Nanostructured liquid characterization unit expoke about Nano-emulsion-derived polymeric carriers for biomedical applications also discussing the impact of the protein corona on colloidal stability, antioxidant activities, cytotoxicity and cellular uptake of drug-loaded nanoparticles.

Antoni Llopis Lorente, (NANBIOSIS U26 NMR: Biomedical Applications II), expoke about Gated silica nanoparticles for controlled release. Chemical communication, based on the exchange of molecules as messengers, allows different entities to share information, cooperate and orchestrate collective behaviors. Communication using chemical messengers (such as neurotransmitters, hormones and pheromones) is the main way of communication across the natural world; yet engineering chemical communication between micro/nanosystems is a key emergent topic in micro/nanotechnology, biomimicry and related areas. Santiago explainined recent progress by their group in the development of engineered particles for chemical communication and nanomedicine applications.

And closing the session, Mariana Köber (Nanomol Group –NANBIOSIS U6 of Biomaterial Processing and Nanostructuring Unit  from CIBER-BBN and ICMAB-CSIC) gave a talk on Quatsomes as versatile nanovesicles for biomedical applications.

In the session of Applications for Oncology, Pilar Martín Duque from NFP group – NANBIOSIS U9 Synthesis of Nanoparticles Unit of CIBER-BBN and INMA-CSIC, gave a very interesting talk explained their approach and recent progress on the search of trojan horses for an improved theragnosis of cancer.

Here we want to thank the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) for hosting this event and for the help in its preparation and development.

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1st Forum of CIBER-BBN/NANBIOSIS and CSIC Nanomed Conection researchers

The Nanomed Conection of the Spanish Research Council (CSIC) and the Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), together with its singular infrastructure NANBIOSIS, have organised a Forum on Nanomedicine Research during the days 30 of June and 1st of July to be held at the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) in Barcelona. The event will be also transmitted on-line previous registration.

This is the first meeting gathering together scientists from CIBER-BBN and its ICTS NANBIOSIS and from the CSIC’ Nanomed Conection with a shared interest in Nanomedicine.

This two days meeting will allow researchers to present their works in progress, share their scientific concerns and needs and discuss the impact of nanomedicine in the emerging fields of drug delivery, diagnosis and therapy.

The programe, available in the web of the forum includes these sessions:

  • Nanobiotechnological solutions for diagnosis and therapy
  • Drug delivery nanosystems
  • Applications for oncology (I and II)
  • Nanomedicine & other frontier applications

Attendance to the Forum (in person / or online) is free prior registration in the web of the forum (following this link):

Registration will remain open until June 26.
We hope to see you there!

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Women in the fight against breast cancer: Ibane Ibasolo

The International Day of Women and Girls in Science on February 11 honor women’s significant achievements in science and place a much-needed focus on girls entering Science, Technology, Engineering, and Mathematics (STEM) careers.

We want to take this day to congratulate all the women scientists, especially our scientists at NANBIOSIS ICTS. Some of them take an active role in the dissemination of research results and reseach contribution to the society, as Dr. Ibane Abasolo who last week participated in different events to explain her team work in the figth against breast cancer.

Ibane Abasolo is the Scientific Coordinator of NANBIOSIS U20 and also the leader of the Drug Delivery & Targeting group of the CIBER-BBN at the Vall d’Hebron Research Institute (VHIR) which coordinates the unit 20 of NANBIOSIS, a team composed mainly by women.

The group cooworks to improve cancer treatment through the development of nanoparticles specially directed towards breast cancer stem cells. These cells are the ones that, despite dividing slowly, give rise to the differentiation of the rest of the tumor cells and are also the most resistant to conventional antitumor treatments.

That is why the group seeks to attack these cells in three ways:

i) selected drugs that induce the differentiation of tumor stem cells into more differentiated cells (and easier to treat),

2) using mechanisms to evade the efflux pumps of drugs and

3) targeting the nanoparticles specifically towards tumor stem cells by using targeting agents (ie antibodies) against antigens on the surface of tumor stem cells.

Dr. Abasolo has illustrated these three approaches by citing papers published in her group during 2021, in which the ICTS Nanbiosis U20 has also directly participated:

Gustavo Carreño, Alfredo Pereira, Fabián Ávila-Salas, Adolfo Marican, Fernanda Andrade, Maria Mercé Roca-Melendres, Oscar Valdés, Sekar Vijayakumar, Simó Schwartz, Ibane Abasolo, Diana Rafael, Esteban F. Durán-Lara, Development of “on-demand” thermo-responsive hydrogels for anti-cancer drugs sustained release: Rational design, in silico prediction and in vitro validation in colon cancer models, Materials Science and Engineering: C, Volume 131, 2021, 112483, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112483.

Yolanda Fernández, Julie Movellan,Laia Foradada, Vanessa Giménez, Natalia García-Aranda, Sandra Mancilla, Ana Armiñán, Sven Even Borgos, Astrid Hyldbakk, Anna Bogdanska, Oliviero L. Gobbo, Adriele Prina-Mello, Jessica Ponti, Luigi Calzolai, Oleksandr Zagorodko, Elena Gallon, Amaya Niño-Pariente, Alison Paul, Simó Schwartz Jr, Ibane Abasolo, María J. Vicent In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy. Adv Healthc Mater. 2021 Oct 27;e2101544. doi: 10.1002/adhm.202101544.

Diana Rafael, Maria Mercè Roca Melendres, Fernanda Andrade, Sara Montero, Francesc Martinez-Trucharte, Mireia Vilar-Hernandez, Esteban Francisco Durán-Lara, Simó Schwartz Jr, Ibane Abasolo,
Thermo-responsive hydrogels for cancer local therapy: Challenges and state-of-art, International Journal of Pharmaceutics, Volume 606, 2021,
120954, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2021.120954.

Marwa M Abu-Serie , Fernanda Andrade, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Diana Rafael, Zamira V Díaz-Riascos, Petra Gener, Ibane Abasolo, Simó Schwartz Jr Pluronic F127 micelles improve the stability and enhance the anticancer stem cell efficacy of citral in breast cancer. Nanomedicine VOL. 16, NO. 17. 2021 Jul;16(17):1471-1485. doi: 10.2217/nnm-2021-0013.

Eva Espinosa-Cano, Miguel Huerta-Madroñal, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Simo Schwartz, Ibane Abasolo, Julio San Román, Maria Rosa Aguilar, Hyaluronic acid (HA)-coated naproxen-nanoparticles selectively target breast cancer stem cells through COX-independent pathways, Materials Science and Engineering: C, Volume 124, 2021, 112024, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112024.

Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernández, Sara Montero, Francesc Martínez-Trucharte, Joaquin Seras-Franzoso, Zamira V. Díaz-Riascos, Ana Boullosa, Natalia García-Aranda, Patricia Cámara-Sánchez, Diego Arango, Marika Nestor, Ibane Abasolo, Bruno Sarmento, Simó Schwartz, Polymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo, Journal of Controlled Release, Volume 331, 2021, 198-212, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.01.022.

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Best Emergeging Researcher Award in the Biomedical Area to Edorta Santos

Edorta Santos Vizcaíno has been awarded as Best Emerging Researcher in the biomedical area by the Bioaraba Health Research Institute in the XXII edition of the Research and Innovation Conference.

This award aims to recognize the work of researchers under the age of 40 who carry out their research activity in any public center of the Araba Health Network (OSI ARABA UNIVERSITY HOSPITAL / BIOARABA). The main award´’s criteria are the quality of the research carried out, active participation in public and private research projects, fidelity to the line of biomedical research and the usefulness and interest of the research developed for the environment are valued. The award also carries a financial endowment destined to continue promoting the research career of the awarded person.

Edorta Santos Vizcaíno (NANBIOSIS Unit 10 “Drug Formulation”) has a degree in Biochemistry and a doctorate in Pharmacy, with an international mention and an extraordinary award, from the UPV / EHU. He has been part of the research group NanoBioCel of the UPV / EHU, Consolidated Group of Excellence of the Basque university system, since 2006. In the same way, he is a member of the Center for Biomedical Research in Network for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), a consortium dependent on the Carlos III Health Institute through the Ministry of Science and Innovation, and the Bioaraba Health Research Institute. Edorta has extensive experience in cell therapy and drug delivery systems. During the last years, his research has focused on the biomedical application of different biomaterials (for example, alginate, gelatin, collagen), mesenchymal stem cells (MSC) and their secretome (extracellular vesicles and soluble factors), in order to exert a immunomodulatory and regenerative effect in the treatment of immune-mediated inflammatory diseases (for example, inflammatory bowel disease, IBD) and the regeneration of chronic wounds, among other applications.

Bioaraba‘s mission is to develop research and innovation of excellence and quality that allows the translation of its results aimed at solving the health problems of the population, also promoting scientific research and for this, it annually carries out the Research and Innovation Conference.

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Study of new liposomes for the delivery of enzymes through biological membranes

Judit Tomsen, researcher at Nanomol Group – NANBIOSIS U6 (ICMAB-CSIC and CIBER-BBN)  will defend her PhD thesis on Thursday, 15 July 2021, at 11 am in an hybrid session, from the ICMAB Seminar Room “Carles Miravitlles”. 

Further information and Registration to attend the PhD Thesis defense via Zoom  at ICMAB-website.

Supervisors:

Nora Ventosa (Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit and leader of Nanomol Group of CIBER-BBN- ICMAB-CSIC

Elisabet González, Nanomol Group of CIBER-BBN – ICMAB-CSIC

Abstract: Liposomes are lipid-based nanovesicles widely explored as nanocarriers for the transport of biomolecules or drugs of interest to the place of action, and for the development of new nanomedicines. This Thesis is devoted to the study of liposomal systems functionalized with targeting-ligands, with the final goal to be used as nanocarriers of therapeutically active enzymes. The new liposomal formulations have been specifically investigated and developed for the effective transportation of α-galactosidase A enzyme through cellular and blood-brain membranes, and for the achievement of a new liposomal intravenous pharmaceutical product candidate (nanoGLA) for the treatment of Fabry disease. The achieved results support the strong potential of targeted liposomal systems for drug delivery application. The successful development and optimization of the nanoGLA product for improving the current enzymatic replacement therapy in Fabry disease especially contributes as an example of translational and interdisciplinary research.

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Identification of a novel nanotherapy active in cancer cells resistant to chemotherapy

Researchers of the Nanotoxicology Unit (u18-nanotoxicology-unit) led by Ramon Mangues and Isolda Casanova at the Research Institute of the Hospital de Sant Pau and the 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, both belonging to the ICTS NANBIOSIS (nanbiosis.es) of the CIBER-BBN, have participated in the production of a novel Nanotoxin capable of selectively killing cancer cells which became resistant to chemotherapy. Development of cancer resistance frequently associates with the overexpression of the CXCR4 receptor.

It is known that chemotherapy kills cancer cells, mainly, by induction of apoptosis, after damaging the cell DNA; therefore, to survive resistant cancer cells develop anti-apoptotic mechanisms. In contrast, a Nanotoxin that has incorporated the exotoxin of Corynebacterium diphtheriae and a targeted ligand that selectively internalizes in CXCR4+ cancer cells, exploits a mechanism of cell death alternative to apoptosis, thus, effectively killing resistant cancer cells in a colorectal cancer model.  The new mechanism is the induction of a blockade of protein translation, by inhibition of the elongation factor 2, which renders sensitive to therapy cancer cells resistant to chemotherapy.

The described work opens a new avenue for the exploration of antitumor activity in cancer that relapses after current therapy, an unmet medical need in oncology, and therefore, it could have an important impact in cancer patient well being.

Reference:

Naroa Serna, Patricia Álamo, Prashanthi Ramesh, Daria Vinokurova, Laura Sánchez-García, Ugutz Unzueta, Alberto Gallardo, María Virtudes Céspedes, Esther Vázquez, Antonio Villaverde, Ramón Mangues, Jan Paul Medema. Nanostructured toxins for the selective destruction of drug-resistant human CXCR4 + colorectal cancer stem cells. doi: 10.1016/j.jconrel.2020.01.019.

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New patented peptide to allows the faster internalization of drugs within cells and the design of more effective therapeutic nanoconjugates

Researchers of NANBIOSIS Unit 20 In vivo Experimental Platform of CIBER-BBN and Vall d’Hebron Research Institute (VHIR) have patented a peptide that, in comparison to the current standard treatment, is much faster, internalizes much more, and does not cause any toxicity.

The membrane of a cell is an effective barrier that hinders the targeted delivery of molecules, such as therapeutic compounds. During the last years, several strategies have been developed to get the molecules into the cell interior but, in general, the methods developed still show a low efficacy and / or toxicity. “The use of therapeutic nanoconjugates such as nanomedicines facilitates the transport and delivery of drugs in target cells, but often with less efficiency than we would like,” says Dr Simó Schwart Jr, head of the Scientific Director of NANBIOSIS Unit 20 and the CIBBIM-Nanomedicine group: Direction i Alliberament Farmacològic del Vall d’Hebron Research Institute (VHIR)/CIBER-BBN.

Given the need to get more drugs or proteins into cells, one of the alternatives to be able to increase the amount that enters their interior more quickly is what is known as Cell penetrating peptides or cellular internalizing peptides, small sequences of amino acids that have the ability to interact with the plasma membranes of cells and, as a result of this interaction, make it easier to internalize the cargo they carry. An example of application would be when an internalizing peptide binds to a therapeutic nanoconjugate, achieving a greater capacity for the nanoconjugate to enter the cell interior and, therefore, to release the drugs it carries into the cells.

Until now, one of the most important internalizing peptides used has been known as TAT. Now, a team of researchers led by Dr. Schwartz Jr, has discovered a sequence common to a family of peptides that significantly outperforms the TAT results and facilitates the cellular internalization of nanoconjugates in a very significant way. These peptides are derived from a membrane protein called CD300 which has a very high capacity to interact with sphingomyelin, a lipid found in all plasma membranes and also in intracellular organelles. “The peptides in our patent”, explains Dr. Simó Schwartz Jr, “are derived from an extracellular part of CD300, which has a high capacity to bind sphingomyelin. Compared to the current standard treatment, TAT, CD300f7 is much faster, internalizes much more, and does not cause any toxicity. The use of these peptides in nanomedicine therefore facilitates and increases the internalization process of all the cargo they carry. This means that we are able to introduce drugs into cells in less time and in greater quantities ”. The results of this discovery not only allow for faster internalization within the cell, but also open the door to designing much more effective therapeutic nanoconjugates.

Souce of information: VHIR news

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New nanocarrier for bio-imaging and drug-delivery applications

Researchers of CIBER-BBN and NANBIOSIS-ICTS (U6 Biomaterial Processing and Nanostructuring Unit at ICMAB-CSIC and U18 Nanotoxicology Unit at  Hospital de la Santa Creu i Sant Pau have developed a new nanocarrier for bio-imaging and drug-delivery applications

The new nanovesicle formulation is based on the quatsome architecture – which stands out due to the high colloidal stability and homogeneity in size – and has now been shown to be suitable for in vivo dosing.

Quatsomes are new non-liposomal lipid-based nanovesicles that have been developed by Nanomol group in recent years, and have been shown to be highly homogeneous and stable in different media for years. This colloidal stability involves important advantages for the development of pharmaceutical formulations and for guaranteeing the final product quality. Quatsomes are a promising nanocarrier for bio-imaging and drug-delivery applications, suitable for the encapsulation of both hydrophilic and hydrophobic molecules, easily functionalized with elements that favor the directionality towards therapeutic targets.

To facilitate their use in in vivo applications, Nanomol group has now developed a new Quatsome formulation, composed of cholesterol and myristalkonium chloride (MKC), the C14 homolog of benzalkonium chloride (BAK), the latter being extensively used as antimicrobial preservative in many ophthalmic and parenteral formulations on the EU and USA market. These novel MKC-Quatsomes have been synthesized in different media that are suitable for parenteral administration, in which they showed to be stable for at least 18 months. Moreover, vesicles remained stable in human serum for at least 24 hours.

In collaboration with the Oncogenesis and Antitumour Drug group of the Biomedical Research Institute of the Hospital de la Santa Creu i Sant Pau, these MKC-Quatsomes were tested in live mice bearing xenografted colorectal tumors. After intravenous injection of fluorescently labelled MKC-Quatsomes, biodistribution assays showed nanovesicle accumulation in tumors, liver, spleen, and kidneys, but not in any other organ. Importantly, MKC-Quatsomes were well-tolerated at the administered doses, and no histological alterations or toxicity was found in any of these organs. These new results suggest the applicability of quatsomes in therapeutic approaches that require systemic delivery.

NANOMOL group, Coordinator of NANBIOSIS U6 at ICMAB-CSIC and the Oncogenesis and Antitumor Drug group, coordinator NANBIOSIS U18 at Biomedical Research Institute (Hospital de la Santa Creu i Sant Pau) are members of Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and have a wide expertise and recognized excellence in the synthesis, processing and study of molecular and polymeric materials and the study of their biomedical properties. NANOMOL is also a member of the technology transfer network TECNIO. ‘

Article of reference:

MKC-Quatsomes. A stable nanovesicle platform for bio-imaging and drug-delivery applications co-authored by Guillem Vargas-Nadal et al., Nanomedicine: Nanotechnology, Biology and Medicine, 24 (2020) 102136. https://doi.org/10.1016/j.nano.2019.102136

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