Enhanced Cytotoxic Effect of Doxorubicin Conjugated to Glutathione-Stabilized Gold Nanoparticles in Canine Osteosarcoma—In Vitro Studies
Anna Małek,
Bartłomiej Taciak,
Katarzyna Sobczak,
Agnieszka Grzelak,
Michał Wójcik,
Józef Mieczkowski,
Roman Lechowski,
Katarzyna A. Zabielska-Koczywąs
Affiliations
Anna Małek
Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
Bartłomiej Taciak
Department of Cancer Biology, Institute of Biology, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland
Katarzyna Sobczak
Laboratory of Organic Nanomaterials and Biomolecules, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
Agnieszka Grzelak
Laboratory of Organic Nanomaterials and Biomolecules, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
Michał Wójcik
Laboratory of Organic Nanomaterials and Biomolecules, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
Józef Mieczkowski
Laboratory of Organic Nanomaterials and Biomolecules, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
Roman Lechowski
Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
Katarzyna A. Zabielska-Koczywąs
Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
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.
