Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells
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2014
Authors
Čolić, Miodrag
Dzopalić, Tanja

Tomić, Sergej

Rajković, Jelena
Rudolf, Rebeka
Vuković, Goran D.
Marinković, Aleksandar

Uskoković, Petar

Article (Published version)

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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, 273-287Publisher:
- 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
Institution/Community
Tehnološko-metalurški fakultetTY - 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 . .