Smaller CpG-Conjugated Gold Nanoconstructs Achieve Higher Targeting Specificity of Immune Activation

Jun Yue, Roger M. Pallares, Lisa E. Cole, Emma E. Coughlin, Chad A. Mirkin, Andrew Lee, Teri W. Odom*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

This study describes a side-by-side comparison of the in vitro immunostimulatory activity of cytosine-phosphate-guanine (CpG)-conjugated gold nanoparticles. Three different gold nanoparticle cores (13 nm spheres, 50 nm spheres, and 40 nm stars) with the same CpG surface density were investigated for toll-like receptor 9 activation. For this parameter set, 13 nm spheres displayed significantly higher specificity for targeting immune receptors and larger nanoparticles (50 nm spheres and 40 nm stars) showed higher cellular uptake and higher immune activation because of off-target effects. Changes in nanoparticle size and presentation of activating ligands affect construct-induced immune responses at different levels, and care must be taken when considering practical and global design rules for CpG delivery.

Original languageEnglish (US)
Pages (from-to)21920-21926
Number of pages7
JournalACS Applied Materials and Interfaces
Volume10
Issue number26
DOIs
StatePublished - Jul 5 2018

Funding

This study was supported by the National Cancer Institute of the National Institutes of Health under Award Number U54CA199091 (J.Y., R.M.P., C.A.M., A.L., T.W.O.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. L.E.C. acknowledges support from Northwestern University’s Cancer Nanotechnology Training Program Award T32CA186897. All plate-based fluorescence and absorbance readings were carried out in the High Throughput Analysis Laboratory. Confocal fluorescence imaging and TEM were performed at the Biological Imaging Facility. Gold analysis was conducted at the Northwestern University Quantitative Bio-elemental Imaging Center generously supported by NASA Ames Research Center NNA06CB93G.

Keywords

  • CpG
  • cellular uptake
  • gold nanoparticles
  • immunostimulatory activity
  • targeting

ASJC Scopus subject areas

  • General Materials Science

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