SPAtially-Controlled lIgand arraNGement by origami-based nanoprinters

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 NPs 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)