Manipulating immune activation of macrophages by tuning the oligonucleotide composition of gold nanoparticles

Roger M. Pallares; Priscilla Choo; Lisa E. Cole; Chad A. Mirkin; Andrew Lee; Teri W. Odom

doi:10.1021/acs.bioconjchem.9b00316

Manipulating immune activation of macrophages by tuning the oligonucleotide composition of gold nanoparticles

Roger M. Pallares, Priscilla Choo, Lisa E. Cole, Chad A. Mirkin, Andrew Lee, Teri W. Odom^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

This paper describes how the ligand shell containing immunostimulatory oligonucleotides surrounding gold nanoparticles affects the in vitro activation of macrophages. Nanoconstructs with similar ligand densities but different oligonucleotide compositions (from 0% to 100% immune-active cytosine-phosphate-guanine, CpG) were compared. Maximum immunostimulation was achieved with CpG content as low as 5% (with total oligonucleotide surface coverage remaining constant), correlating to high levels of antitumor cytokine release and low levels of cancer-promoting ones. Independent of CpG content, gold nanoparticles with low oligonucleotide densities exhibit poor cellular uptake, leading to insignificant immunostimulation and cytokine release. By identifying effects of ligand shell composition on macrophage activation, we can inform the design rules of therapeutic nanoconstructs to achieve specific immune responses.

Original language	English (US)
Pages (from-to)	2032-2037
Number of pages	6
Journal	Bioconjugate Chemistry
Volume	30
Issue number	7
DOIs	https://doi.org/10.1021/acs.bioconjchem.9b00316
State	Published - Jul 17 2019

ASJC Scopus subject areas

Bioengineering
Biotechnology
Biomedical Engineering
Pharmacology
Pharmaceutical Science
Organic Chemistry

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Manipulating immune activation of macrophages by tuning the oligonucleotide composition of gold nanoparticles",

abstract = "This paper describes how the ligand shell containing immunostimulatory oligonucleotides surrounding gold nanoparticles affects the in vitro activation of macrophages. Nanoconstructs with similar ligand densities but different oligonucleotide compositions (from 0% to 100% immune-active cytosine-phosphate-guanine, CpG) were compared. Maximum immunostimulation was achieved with CpG content as low as 5% (with total oligonucleotide surface coverage remaining constant), correlating to high levels of antitumor cytokine release and low levels of cancer-promoting ones. Independent of CpG content, gold nanoparticles with low oligonucleotide densities exhibit poor cellular uptake, leading to insignificant immunostimulation and cytokine release. By identifying effects of ligand shell composition on macrophage activation, we can inform the design rules of therapeutic nanoconstructs to achieve specific immune responses.",

author = "Pallares, {Roger M.} and Priscilla Choo and Cole, {Lisa E.} and Mirkin, {Chad A.} and Andrew Lee and Odom, {Teri W.}",

note = "Funding Information: The scientific work reported in this article has been supported by the National Cancer Institute of the National Institutes of Health under Award Number U54CA199091 (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{\textquoteright}s Cancer Nanotechnology Training Program Award T32CA186897. A.L. and C.A.M. acknowledge support from the Prostate Cancer Foundation and the Movember Foundation under award 17CHAL08. Fluorescence spectroscopy was performed at the High Throughput Analysis Laboratory. Quantification of gold was conducted at the Northwestern University Quantitative Bioelemental Imaging Center generously supported by NASA Ames Research Center NNA06CB93G. Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

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AB - This paper describes how the ligand shell containing immunostimulatory oligonucleotides surrounding gold nanoparticles affects the in vitro activation of macrophages. Nanoconstructs with similar ligand densities but different oligonucleotide compositions (from 0% to 100% immune-active cytosine-phosphate-guanine, CpG) were compared. Maximum immunostimulation was achieved with CpG content as low as 5% (with total oligonucleotide surface coverage remaining constant), correlating to high levels of antitumor cytokine release and low levels of cancer-promoting ones. Independent of CpG content, gold nanoparticles with low oligonucleotide densities exhibit poor cellular uptake, leading to insignificant immunostimulation and cytokine release. By identifying effects of ligand shell composition on macrophage activation, we can inform the design rules of therapeutic nanoconstructs to achieve specific immune responses.

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Manipulating immune activation of macrophages by tuning the oligonucleotide composition of gold nanoparticles

Abstract

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