RT Journal Article
SR Electronic
T1 Determinants of ligand-functionalized DNA nanostructure-cell interactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.24.432702
DO 10.1101/2021.02.24.432702
A1 Glenn A.O. Cremers
A1 Bas J.H.M. Rosier
A1 Ab Meijs
A1 Nicholas B. Tito
A1 Sander M.J. van Duijnhoven
A1 Hans van Eenennaam
A1 Lorenzo Albertazzi
A1 Tom F.A. de Greef
YR 2021
UL http://biorxiv.org/content/early/2021/02/24/2021.02.24.432702.abstract
AB Synthesis of ligand-functionalized nanomaterials with control over size, shape and ligand orientation, facilitates the design of tailored nanomedicines for therapeutic purposes. DNA nanotechnology has emerged as a powerful tool to rationally construct two- and three-dimensional nanostructures, enabling site-specific incorporation of protein ligands with control over stoichiometry and orientation. To efficiently target cell surface receptors, exploration of the parameters that modulate cellular accessibility of these nanostructures is essential. In this study we systematically investigate tunable design parameters of antibody-functionalized DNA nanostructures binding to therapeutically relevant receptors. We show that, although the native affinity of antibody-functionalized DNA nanostructures remains unaltered, the absolute number of bound surface receptors is lower compared to soluble antibodies and is mainly governed by nanostructure size and DNA handle location. The obtained results provide key insights in the ability of ligand-functionalized DNA nanostructures to bind surface receptors and yields design rules for optimal cellular targeting.Competing Interest StatementThe authors have declared no competing interest.