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Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells

Authorized Users Only
2014
Authors
Čolić, Miodrag
Dzopalić, Tanja
Tomić, Sergej
Rajković, Jelena
Rudolf, Rebeka
Vuković, Goran D.
Marinković, Aleksandar
Uskoković, Petar
Article (Published version)
Metadata
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Abstract
The protocols for the preparation of dendritic cells (DCs) as cancer vaccines based on stimulation of Toll-like receptors (TLRs) are very promising. In this study we covalently attached 7-thia-8-oxoguanosine (7-TOG), a selective endosomal TLR7, to previously oxidized multi-walled carbon nanotubes (o-MWCNTs) (mass ratio 1:5.6, respectively), and tested their ability to activate human monocyte-derived (Mo)DCs. Light, confocal and transmission electron microscopy confirmed efficient phagocytosis of 7-TOG-MWCNTs by MoDCs and their efficient delivery to TLR7(+) endosomes. The biocompatibility studies showed that 7-TOG-MWCNTs, at concentrations lower than 100 mu g/ml, were not cytotoxic for MoDCs. 7-TOG-MV/CNTs (50 mu g/ml) up-regulated CD86 expression, allostimulatory activity, T helper (Th)1- and Th17-polarizing capability of MoDCs. The same concentration of soluble 7-TOG, alone or in combination with control o-MWCNTs, did not have such effects. It can be hypothesized that the efficacy of ...7-TOG-MWCNTs in stimulating MoDCs was a consequence of increased intracellular concentration of 7-TOG after internalization of the nano-complexes, because similar Th-polarizing capability could be induced with 10-times higher concentrations of soluble 7-TOG. In conclusion, our results suggest that functionalized MWCNTs may be a promising system for the delivery of drugs to intracellular targets, in order to improve the immunogenic potential of DCs for therapeutic purposes.

Source:
Carbon, 2014, 67, 273-287
Publisher:
  • Pergamon-Elsevier Science Ltd, Oxford
Funding / projects:
  • Application of functionalyzed carbon nanotubes and gold nanoparticles for preparation of dendritic cells for tumor therapy (RS-175102)
  • Military Medical Academy, Belgrade [MFVMA/8/12-14]
  • Reinforcing of Nanotechnology and Functional Materials Centre (EU-245916)

DOI: 10.1016/j.carbon.2013.09.090

ISSN: 0008-6223

WoS: 000329379300030

Scopus: 2-s2.0-84892785218
[ Google Scholar ]
19
14
URI
http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2782
Collections
  • Radovi istraživača / Researchers’ publications (TMF)
Institution/Community
Tehnološko-metalurški fakultet
TY  - JOUR
AU  - Čolić, Miodrag
AU  - Dzopalić, Tanja
AU  - Tomić, Sergej
AU  - Rajković, Jelena
AU  - Rudolf, Rebeka
AU  - Vuković, Goran D.
AU  - Marinković, Aleksandar
AU  - Uskoković, Petar
PY  - 2014
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2782
AB  - The protocols for the preparation of dendritic cells (DCs) as cancer vaccines based on stimulation of Toll-like receptors (TLRs) are very promising. In this study we covalently attached 7-thia-8-oxoguanosine (7-TOG), a selective endosomal TLR7, to previously oxidized multi-walled carbon nanotubes (o-MWCNTs) (mass ratio 1:5.6, respectively), and tested their ability to activate human monocyte-derived (Mo)DCs. Light, confocal and transmission electron microscopy confirmed efficient phagocytosis of 7-TOG-MWCNTs by MoDCs and their efficient delivery to TLR7(+) endosomes. The biocompatibility studies showed that 7-TOG-MWCNTs, at concentrations lower than 100 mu g/ml, were not cytotoxic for MoDCs. 7-TOG-MV/CNTs (50 mu g/ml) up-regulated CD86 expression, allostimulatory activity, T helper (Th)1- and Th17-polarizing capability of MoDCs. The same concentration of soluble 7-TOG, alone or in combination with control o-MWCNTs, did not have such effects. It can be hypothesized that the efficacy of 7-TOG-MWCNTs in stimulating MoDCs was a consequence of increased intracellular concentration of 7-TOG after internalization of the nano-complexes, because similar Th-polarizing capability could be induced with 10-times higher concentrations of soluble 7-TOG. In conclusion, our results suggest that functionalized MWCNTs may be a promising system for the delivery of drugs to intracellular targets, in order to improve the immunogenic potential of DCs for therapeutic purposes.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Carbon
T1  - Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells
EP  - 287
SP  - 273
VL  - 67
DO  - 10.1016/j.carbon.2013.09.090
ER  - 
@article{
author = "Čolić, Miodrag and Dzopalić, Tanja and Tomić, Sergej and Rajković, Jelena and Rudolf, Rebeka and Vuković, Goran D. and Marinković, Aleksandar and Uskoković, Petar",
year = "2014",
abstract = "The protocols for the preparation of dendritic cells (DCs) as cancer vaccines based on stimulation of Toll-like receptors (TLRs) are very promising. In this study we covalently attached 7-thia-8-oxoguanosine (7-TOG), a selective endosomal TLR7, to previously oxidized multi-walled carbon nanotubes (o-MWCNTs) (mass ratio 1:5.6, respectively), and tested their ability to activate human monocyte-derived (Mo)DCs. Light, confocal and transmission electron microscopy confirmed efficient phagocytosis of 7-TOG-MWCNTs by MoDCs and their efficient delivery to TLR7(+) endosomes. The biocompatibility studies showed that 7-TOG-MWCNTs, at concentrations lower than 100 mu g/ml, were not cytotoxic for MoDCs. 7-TOG-MV/CNTs (50 mu g/ml) up-regulated CD86 expression, allostimulatory activity, T helper (Th)1- and Th17-polarizing capability of MoDCs. The same concentration of soluble 7-TOG, alone or in combination with control o-MWCNTs, did not have such effects. It can be hypothesized that the efficacy of 7-TOG-MWCNTs in stimulating MoDCs was a consequence of increased intracellular concentration of 7-TOG after internalization of the nano-complexes, because similar Th-polarizing capability could be induced with 10-times higher concentrations of soluble 7-TOG. In conclusion, our results suggest that functionalized MWCNTs may be a promising system for the delivery of drugs to intracellular targets, in order to improve the immunogenic potential of DCs for therapeutic purposes.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Carbon",
title = "Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells",
pages = "287-273",
volume = "67",
doi = "10.1016/j.carbon.2013.09.090"
}
Čolić, M., Dzopalić, T., Tomić, S., Rajković, J., Rudolf, R., Vuković, G. D., Marinković, A.,& Uskoković, P.. (2014). Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells. in Carbon
Pergamon-Elsevier Science Ltd, Oxford., 67, 273-287.
https://doi.org/10.1016/j.carbon.2013.09.090
Čolić M, Dzopalić T, Tomić S, Rajković J, Rudolf R, Vuković GD, Marinković A, Uskoković P. Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells. in Carbon. 2014;67:273-287.
doi:10.1016/j.carbon.2013.09.090 .
Čolić, Miodrag, Dzopalić, Tanja, Tomić, Sergej, Rajković, Jelena, Rudolf, Rebeka, Vuković, Goran D., Marinković, Aleksandar, Uskoković, Petar, "Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells" in Carbon, 67 (2014):273-287,
https://doi.org/10.1016/j.carbon.2013.09.090 . .

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