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56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

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Braintumor-uptake of Antisense-oligonucleotides against TGF-beta2, after coupling with nanoparticles coated with Polysorbate 80 in a rat glioma model

Aufnahme von Antisenseoligonukleotiden gegen TGF-beta2 in Hirntumoren nach Bindung an Nanopartikel ummantelt mit Polysorbat 80 im Rattengliommodell

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  • corresponding author A. Becker - Klinik für Neurochirurgie, Otto-von-Guericke-Universität, Magdeburg
  • C. Walz, - Institut fürMedizinische Psychologie, Otto-von-Guericke-Universität, Magdeburg
  • C. Mawrin - Institut für Neuropathologie, Otto-von-Guericke-Universität, Magdeburg
  • R. Firsching - Klinik für Neurochirurgie, Otto-von-Guericke-Universität, Magdeburg
  • T. Schneider - Klinik für Neurochirurgie, Otto-von-Guericke-Universität, Magdeburg

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP157

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2005/05dgnc0425.shtml

Published: May 4, 2005

© 2005 Becker et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

Especially because of its immunosuppression TGF-beta2 is held for one of the important growth factors produced by glioblastoma. Antisense-oligonucleotides should be a propriate instrument to inhibit the cytokine-production of glioblastoma cells, but they poorly penetrate the blood-brain-barrier. Polybutylcanoacrylate-Nanoparticles could be used as a carrier system transporting for instance peptides over the blood-brain-barrier. In a rat glioma model the intratumoral uptake of antisense-oligonucleotides against TGF-beta was determined after pure peripheral application in comparison to application after coupling with nanoparticles and coating with Polysorbate 80.

Methods

In Fisher rats (2 groups of 6 rats) a glioblastoma was induced by inoculation of F98 cells in the right caudate nucleus. 12 days after implantation the rats were treated in one group with i.p. injection of FITC-labeled antisense oligonucleotides against TGF-beta2 (10 nmol) coupled to nanoparticles and coated with Polysorbate 80. In the other group the pure antisense were injected. Six hours later all animals were sacrificed and brains were examined. The amount of FITC-labeled tumor-cells was determined immunhistochemically.

Results

By combination of antisense-oligonucleotides with nanoparticles the intratumoral amount of labeled cells was significantly increased for 67,5%. While in animals treated only with oligonucleotides (control-group) no labeled cells were seen outside the glioma tissue, a number of cells with an uptake of FITC were found as well in normal tissue after application of antisense-oligonucleotides-nanoparticles. No significant side effects of nanoparticles did appear in this very short time after application.

Conclusions

Nanoparticles coated with Polysorbate 80 may work as a carrier system for Antisense-oligonucleotides against TGF-beta2 crossing the blood-brain-barrier in this animal glioma model. The application of this Antisense-oligonucleotides coupled to nanoparticles may be considered another approach of glioblastoma therapy, either alone or in combination with some kind of immunotherapy.