Enhanced Cytotoxic Effect of Doxorubicin Conjugated to Glutathione-Stabilized Gold Nanoparticles in Canine Osteosarcoma—In Vitro Studies
Autor: | Anna Małek, Bartłomiej Taciak, Katarzyna Sobczak, Agnieszka Grzelak, Michał Wójcik, Józef Mieczkowski, Roman Lechowski, Katarzyna A. Zabielska-Koczywąs |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: | |
Zdroj: | Molecules, Vol 26, Iss 12, p 3487 (2021) |
Druh dokumentu: | article |
ISSN: | 26123487 1420-3049 |
DOI: | 10.3390/molecules26123487 |
Popis: | Osteosarcoma (OSA) is the most common malignant bone neoplasia in humans and dogs. In dogs, treatment consists of surgery in combination with chemotherapy (mostly carboplatin and/or doxorubicin (Dox)). Chemotherapy is often rendered ineffective by multidrug resistance. Previous studies have revealed that Dox conjugated with 4 nm glutathione-stabilized gold nanoparticles (Au-GSH-Dox) enhanced the anti-tumor activity and cytotoxicity of Dox in Dox-resistant feline fibrosarcoma cell lines exhibiting high P-glycoprotein (P-gp) activity. The present study investigated the influence of Au-GSH-Dox on the canine OSA cell line D17 and its relationship with P-gp activity. A human Dox-sensitive OSA cell line, U2OS, served as the negative control. Au-GSH-Dox, compared to free Dox, presented a greater cytotoxic effect on D17 (IC50 values for Au-GSH-Dox and Dox were 7.9 μg/mL and 15.2 μg/mL, respectively) but not on the U2OS cell line. All concentrations of Au-GSH (ranging from 10 to 1000 μg/mL) were non-toxic in both cell lines. Inhibition of the D17 cell line with 100 μM verapamil resulted in an increase in free Dox but not in intracellular Au-GSH-Dox. The results indicate that Au-GSH-Dox may act as an effective drug in canine OSA by bypassing P-gp. |
Databáze: | Directory of Open Access Journals |
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