Glucoheptoamidated polyamidoamine PAMAM G3 dendrimer as a vehicle for succinate linked doxorubicin; enhanced toxicity of DOX against grade IV glioblastoma U-118 MG cells
| Autor: | Konrad Kwaśniak, Łukasz Uram, Iwona Filiks, Justyna Czarnik-Kwaśniak, Monika Stompor, Stanisław Wołowiec, Krzysztof Tutaj |
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| Rok vydání: | 2020 |
| Předmět: |
Chemistry
Pharmaceutical Science 02 engineering and technology 021001 nanoscience & nanotechnology medicine.disease 030226 pharmacology & pharmacy Molecular biology 03 medical and health sciences 0302 clinical medicine Dendrimer Glioma Toxicity medicine Peptide bond Doxorubicin 0210 nano-technology Linker IC50 Conjugate medicine.drug |
| Zdroj: | Journal of Drug Delivery Science and Technology. 55:101424 |
| ISSN: | 1773-2247 |
| Popis: | Glioblastoma multiforme (GBM), known as astrocytoma grade IV, is the most common primary malignant brain tumor and one of the most lethal forms of cancer with a median survival rate of approximately 15 months after standard treatment. Currently, the chance of increasing the survival rate is found in therapy with doxorubicin (DOX) delivered to the central nervous system by polymeric carriers. In this study, we synthesized and characterized by NMR spectroscopy, a vehicle for DOX based on glucoheptoamidated poly (amidoamine) dendrimers of third generation (G3gh) and its derivative substituted with 4 residues of DOX attached via succinate linkers (G3gh4DOX). The pH dependent DOX release profile from the well soluble G3gh4DOX indicates a slow release that is significantly higher in an acidic environment due to hydrolytic cleavage of an amide bond between DOX and the succinate linker, not the ester bond between succinate linker and the glucoheptoamide substituent. Biological studies demonstrate efficient grade IV human U-118 MG glioma cells damage by G3gh4DOX conjugates at very low concentrations, with IC50 |
| Databáze: | OpenAIRE |
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