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Tumor targeting with pH-responsive poly(2-oxazoline)-based nanogels for metronomic doxorubicin treatment

Title data

Hoelzer, Doerte ; Leiske, Meike N. ; Hartlieb, Matthias ; Bus, Tanja ; Pretzel, David ; Hoeppener, Stephanie ; Kempe, Kristian ; Thierbach, René ; Schubert, Ulrich S.:
Tumor targeting with pH-responsive poly(2-oxazoline)-based nanogels for metronomic doxorubicin treatment.
In: Oncotarget. Vol. 9 (2018) Issue 32 . - pp. 22316-22331.
ISSN 1949-2553
DOI: https://doi.org/10.18632/oncotarget.24806

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: poly(2-oxazoline); doxorubicin; drug delivery; nanogel; metronomic
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Junior Professor Sustainable and Functional Polymer Systems > Junior Professor Sustainable and Functional Polymer Systems - Juniorprof. Dr. Meike Leiske
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Junior Professor Sustainable and Functional Polymer Systems
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 18 Jan 2023 14:47
Last Modified: 13 Mar 2023 08:44
URI: https://eref.uni-bayreuth.de/id/eprint/73455