Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Yuvaraj Manoharan,1,* Qingmin Ji,2,* Tomohiko Yamazaki,2,3 Shanmugavel Chinnathambi,1 Song Chen,2,4 Ganesan Singaravelu,1 Jonathan P Hill,2 Katsuhiko Ariga,2,5 Nobutaka Hanagata3,6 1Department of Medical Physics, Anna University, Chennai, India; 2Research Center for Materials Nanoarchitectonics, Nat...

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Autores principales: Manoharan Y, Ji Q, Yamazaki T, Chinnathambi S, Chen S, Ganesan S, Hill JP, Ariga K, Hanagata N
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:1384c888da2d49ad992084548c8bc5252021-12-02T00:39:55ZEffect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α1176-91141178-2013https://doaj.org/article/1384c888da2d49ad992084548c8bc5252012-07-01T00:00:00Zhttp://www.dovepress.com/effect-of-molecular-weight-of-polyethyleneimine-on-loading-of-cpg-olig-a10414https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yuvaraj Manoharan,1,* Qingmin Ji,2,* Tomohiko Yamazaki,2,3 Shanmugavel Chinnathambi,1 Song Chen,2,4 Ganesan Singaravelu,1 Jonathan P Hill,2 Katsuhiko Ariga,2,5 Nobutaka Hanagata3,6 1Department of Medical Physics, Anna University, Chennai, India; 2Research Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibarak, 3Graduate School of Life Science, Hokkaido University, Kita-ku, Sapporo, 4JSPS Research Fellow, Chiyoda-ku, Tokyo, 5JST and CREST, National Institute for Materials Science, Tsukuba, Ibaraki, Japan; 6Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Ibaraki, Japan*These authors contributed equally to this workBackground: Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules.Methods: For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO2 nanoparticles were prepared by coating SiO2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da).Results: The capacity of the flake-shell SiO2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.Keywords: CpG oligodeoxynucleotides, polyethyleneimine, Toll-like receptor 9, silica nanoparticles, delivery, interferon-αManoharan YJi QYamazaki TChinnathambi SChen SGanesan SHill JPAriga KHanagata NDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3625-3635 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Manoharan Y
Ji Q
Yamazaki T
Chinnathambi S
Chen S
Ganesan S
Hill JP
Ariga K
Hanagata N
Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
description Yuvaraj Manoharan,1,* Qingmin Ji,2,* Tomohiko Yamazaki,2,3 Shanmugavel Chinnathambi,1 Song Chen,2,4 Ganesan Singaravelu,1 Jonathan P Hill,2 Katsuhiko Ariga,2,5 Nobutaka Hanagata3,6 1Department of Medical Physics, Anna University, Chennai, India; 2Research Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibarak, 3Graduate School of Life Science, Hokkaido University, Kita-ku, Sapporo, 4JSPS Research Fellow, Chiyoda-ku, Tokyo, 5JST and CREST, National Institute for Materials Science, Tsukuba, Ibaraki, Japan; 6Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Ibaraki, Japan*These authors contributed equally to this workBackground: Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules.Methods: For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO2 nanoparticles were prepared by coating SiO2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da).Results: The capacity of the flake-shell SiO2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.Keywords: CpG oligodeoxynucleotides, polyethyleneimine, Toll-like receptor 9, silica nanoparticles, delivery, interferon-α
format article
author Manoharan Y
Ji Q
Yamazaki T
Chinnathambi S
Chen S
Ganesan S
Hill JP
Ariga K
Hanagata N
author_facet Manoharan Y
Ji Q
Yamazaki T
Chinnathambi S
Chen S
Ganesan S
Hill JP
Ariga K
Hanagata N
author_sort Manoharan Y
title Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
title_short Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
title_full Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
title_fullStr Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
title_full_unstemmed Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α
title_sort effect of molecular weight of polyethyleneimine on loading of cpg oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced tlr9-mediated induction of interferon-α
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/1384c888da2d49ad992084548c8bc525
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