Open AccessSpatially Controlled Activation of Toll-like Receptor 9 with DNA-Based Nanomaterials
Author(s) -
Alice Comberlato,
Marianna M. Koga,
Simone Nüssing,
Ian A. Parish,
Maartje M. C. Bastings
Publication year - 2022
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.2c00275
Subject(s) - nanomaterials , biomolecule , immune system , nanotechnology , dna , aptamer , receptor , dna origami , dna nanotechnology , ligand (biochemistry) , chemistry , biophysics , microbiology and biotechnology , toll like receptor 9 , small molecule , computational biology , biology , materials science , biochemistry , immunology , gene , gene expression , dna methylation
First evidence of geometrical patterns and defined distances of biomolecules as fundamental parameters to regulate receptor binding and cell signaling have emerged recently. Here, we demonstrate the importance of controlled nanospacing of immunostimulatory agents for the activation of immune cells by exploiting DNA-based nanomaterials and pre-existing crystallography data. We created DNA origami nanoparticles that present CpG-motifs in rationally designed spatial patterns to activate Toll-like Receptor 9 in RAW 264.7 macrophages. We demonstrated that stronger immune activation is achieved when active molecules are positioned at the distance of 7 nm, matching the active dimer structure of the receptor. Moreover, we show how the introduction of linkers between particle and ligand can influence the spatial tolerance of binding. These findings are fundamental for a fine-tuned manipulation of the immune system, considering the importance of spatially controlled presentation of therapeutics to increase efficacy and specificity of immune-modulating nanomaterials where multivalent binding is involved.