Open AccessEndosomal Organization of CpG Constructs Correlates with Enhanced Immune Activation
Author(s) -
Kwahun Lee,
Ziyin Huang,
Chad A. Mirkin,
Teri W. Odom
Publication year - 2020
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.0c02536
Subject(s) - endosome , tlr9 , cpg site , microbiology and biotechnology , immune system , proinflammatory cytokine , chemokine , chemistry , nanotechnology , biophysics , materials science , biology , inflammation , immunology , intracellular , dna methylation , gene expression , biochemistry , gene
This Letter describes how the endosomal organization of immunostimulatory nanoconstructs can tune the in vitro activation of macrophages. Nanoconstructs composed of gold nanoparticles conjugated with unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides have distinct endosomal distributions depending on the surface curvature. Mixed-curvature constructs produce a relatively high percentage of hollow endosomes, where constructs accumulated primarily along the interior edges. These constructs achieved a higher level of toll-like receptor (TLR) 9 activation along with the enhanced secretion of proinflammatory cytokines and chemokines compared to constant-curvature constructs that aggregated mostly in the center of the endosomes. Our results underscore the importance of intraendosomal interactions in regulating immune responses and targeted delivery.