Tumor targeting with pH-responsive poly(2-oxazoline)-based nanogels for metronomic doxorubicin treatment
| Autor: | Ulrich S. Schubert, René Thierbach, Doerte Hoelzer, Tanja Bus, Stephanie Hoeppener, Kristian Kempe, Meike N. Leiske, David Pretzel, Matthias Hartlieb |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Drug
Biodistribution media_common.quotation_subject 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Micelle doxorubicin metronomic In vivo medicine polycyclic compounds Doxorubicin media_common Chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences poly(2-oxazoline) Oncology Drug delivery drug delivery nanogel 0210 nano-technology Drug carrier medicine.drug Nanogel Research Paper |
| Zdroj: | Hoelzer, D.; Leiske, M.N.; Hartlieb, M.; Bus, T.; Pretzel, D.; Hoeppener, S.; Kempe, K.; Thierbach, R.; Schubert, U.S.: Tumor targeting with pH-responsive poly(2-oxazoline)-based nanogels for metronomic doxorubicin treatment. In: Oncotarget. Vol. 9 (2018) 32, 22316-22331. (DOI: /10.18632/oncotarget.24806) Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The synthesis of a new nanogel drug carrier system loaded with the anti-cancer drug doxorubicin (DOX) is presented. Poly(2-oxazoline) (POx) based nanogels from block copolymer micelles were cross-linked and covalently loaded with DOX using pH-sensitive Schiff' base chemistry. DOX loaded POx based nanogels showed a toxicity profile comparable to the free drug, while unloaded drug carriers showed no toxicity. Hemolytic activity and erythrocyte aggregation of the drug delivery system was found to be low and cellular uptake was investigated by flow cytometry and fluorescence microscopy. While the amount of internalized drug was enhanced when incorporated into a nanogel, the release of the drug into the nucleus was delayed. For in vivo investigations the nanogel drug delivery system was combined with a metronomic treatment of DOX. Low doses of free DOX were compared to equivalent DOX loaded nanogels in a xenograft mouse model. Treatment with POx based nanogels revealed a significant tumor growth inhibition and increase in survival time, while pure DOX alone had no effect on tumor progression. The biodistribution was investigated by microscopy of organs of mice and revealed a predominant localization of DOX within tumorous tissue. Thus, the POx based nanogel system revealed a therapeutic efficiency despite the low DOX concentrations and could be a promising strategy to control tumor growth with fewer side effects. |
| Databáze: | OpenAIRE |
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