Graphene oxide nanocells for impairing topoisomerase and DNA in cancer cells
| Autor: | Sudipta Basu, Chandramouli Ghosh, Aman Bajpai, Aditi Nandi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_class
Biomedical Engineering 02 engineering and technology 010402 general chemistry 01 natural sciences HeLa chemistry.chemical_compound medicine General Materials Science Doxorubicin Cisplatin biology Topoisomerase General Chemistry General Medicine 021001 nanoscience & nanotechnology biology.organism_classification 0104 chemical sciences chemistry Cancer cell Cancer research biology.protein Topotecan 0210 nano-technology Topoisomerase inhibitor DNA medicine.drug |
| Zdroj: | Journal of Materials Chemistry B. 7:4191-4197 |
| ISSN: | 2050-7518 2050-750X |
| Popis: | DNA topoisomerases and nuclear DNA are important targets for cancer therapy. However, DNA topoisomerase inhibitors and DNA damaging drugs demonstrate a large window of side effects in the clinic. Graphene oxide based biocompatible and biodegradable nano-scale materials have the potential to overcome this complication. However, encompassing different topoisomerase inhibitors along with DNA damaging drugs into 2D-graphene oxide remains a main challenge. To address this, in this manuscript, we have engineered self-assembled spherical 3D-graphene oxide nanoparticles coated with lipid (GO-nanocells) which can concomitantly load and release multiple topoisomerase inhibitors (topotecan and doxorubicin) and DNA damaging drug (cisplatin) in a controlled manner. Fluorescence confocal microscopy confirmed that these GO-nanocells were taken up by HeLa cervical cancer cells and transported into lysosomes temporally over 6 h. A combination of confocal microscopy, gel electrophoresis, and flow cytometry studies revealed that these GO-nanocells damaged nuclear DNA along with topoisomerase inhibition leading to induction of apoptosis through cell cycle arrest in the G2-M phase. These GO-nanocells killed HeLa cancer cells with remarkably greater efficacy compared to a free drug cocktail at 48 h post-incubation. These self-assembled GO-nanocells can serve as a nanoscale tool to perturb multiple therapeutically important sub-cellular targets simultaneously for improved efficacy in future cancer chemotherapy. |
| Databáze: | OpenAIRE |
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