Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
| Autor: | Alp, Esma, Damkaci, Fehmi, Guven, Eylem, Tenniswood, Martin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
epigenetics
Cell Cycle apoptosis DNA fragmentation Breast Neoplasms Starch Hydroxamic Acids Histone Deacetylase Inhibitors Drug Liberation Kinetics Solubility International Journal of Nanomedicine gene expression MCF-7 Cells Humans Nanoparticles Female RNA Messenger MCF-7 Tumor Suppressor Protein p53 Original Research |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Esma Alp,1–4 Fehmi Damkaci,2 Eylem Guven,1 Martin Tenniswood3,4 1Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, Ankara 06800, Turkey; 2Department of Chemistry, State University of New York at Oswego, Oswego, NY 13126, USA; 3Cancer Research Center, Rensselaer, NY 12144, USA; 4Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, NY 12144, USA Background: The efficacy of epigenetic drugs, such as histone deacetylase inhibitors, is often diminished by poor aqueous solubility resulting in limited bioavailability and a low therapeutic index. To overcome the suboptimal therapeutic index, we have developed a biocompatible starch nanoparticle formulation of CG-1521, a histone deacetylase inhibitor in preclinical development for hard-to-treat breast cancers, which improves its bioavailability and half-life. Methods: The physicochemical parameters (size, zeta potential, morphology, loading, and release kinetics) of these nanoparticles (CG-NPs) have been optimized and their cytotoxic and apoptotic capacities measured in MCF-7 breast cancer cell line. The mechanism of action of the encapsulated drug was compared with the free drug at molecular level. Results: We show that encapsulation of CG-1521 substantially reduces the release rate of drug and provides a significantly enhanced cytotoxic ability of nanoparticles compared with equivalent dose of free CG-1521. CG-NPs induced cell cycle arrest and significant apoptosis in MCF-7 cells in vitro. The biological action of encapsulated drug has the similar impact with free drug on gene expression.Conclusion: The findings suggest that encapsulation of CG-1521 into starch nanoparticles can improve drug delivery of histone deacetylase inhibitors for breast cancer therapy without interfering with the mechanism of action of the drug. Keywords: cell cycle, apoptosis, DNA fragmentation, gene expression, epigenetics, MCF-7 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|