Artikel
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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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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.