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SPAtially-Controlled lIgand arraNGement by origami-based nanoprinters

Description du projet

Bio-imprimer des nanoparticules pour les applications médicales

L’usage médical des nanotechnologies concerne des applications de nanoparticules pour l’administration de médicaments et le diagnostic. Financé par l’UE, le projet SPACING veut développer une technologie innovante pour la préconception de nanoparticules avec des configurations spécifiques de ligand 3D. Cette approche permet l’impression de ligands sur des nanoparticules dans n’importe quel arrangement spatial souhaité, même celui ressemblant à des capsides de virus. Les chercheurs surveilleront le comportement de trafic de ces nanoparticules bio-inspirées au sein des cellules et évalueront leur potentiel pour éviter la dégradation lysosomale, à l’instar des virus naturels. Dans l’ensemble, la technologie SPACING devrait faire progresser les stratégies actuelles de fabrication de nanoparticules.

Objectif

The key challenge of SPACING is to develop a beyond state-of-the-art technology to self-assemble pre-designed 3D ligand configurations with sub-nanometer precision (nanopatterning) onto colloidal nanoparticles (NPs). The proposed aqueous-based technology is aimed to develop artificial NP´s libraries with a pre-designed discrete number of ligands in any desired spatial arrangement (i.e. inspired by nature such as virus capsids), which so far has not been feasible by any method (in solution or otherwise).
Within this project we will design and develop a versatile, reusable and user-friendly DNA origami-based tool (nanoprinters) for printing ligands onto NPs; the multifunctionality and robustness of the nanoprinters required for such purpose will involve a first stage concerning the fabrication of libraries of NPs (different size and shape), for which we will design and assemble the corresponding libraries of DNA-origamis having pre-designed voids (shape, size, 3D ligand “stamps”).
In a second stage, as a proof of concept inspired by previous knowledge on specific receptor-mediated endocytotic pathways and virus-cell interactions, we will use the nanoprinters to fabricate a discrete number of NPs with specific ligand configurations (ligand ID, number, density and 3D arrangement). The trafficking behavior of these bio-inspired NPs within cells and tissue models, will serve us to correlate their potential escape from endosome (thereby avoiding lysosomal degradation as viruses do).
While the overall mission behind this project is to build the foundation for a technological implementation of artificial NPs with pre-designed 3D ligand configurations, and their potential to escape lysosomal degradation as viruses do, the proposed demonstrations will contribute to advance future developments in nanomedicine (this approach would be easily extended to any nanocarrier), and other applications in which precision is important (e.g.,formation of metamaterials by NPs self-assembly)

Régime de financement

ERC-STG - Starting Grant

Institution d’accueil

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Contribution nette de l'UE
€ 1 498 866,00
Adresse
COLEXIO DE SAN XEROME PRAZA DO OBRADOIRO S/N
15782 Santiago De Compostela
Espagne

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Région
Noroeste Galicia A Coruña
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 498 866,00

Bénéficiaires (1)