| Autor: |
Hoang Michael Nguyen, Shanzay Chaudhry, Tarun K. Mandal, Anup K. Kundu, Sruti Chandra, Nicholas Hall, George Olverson, Kylar Wiltz, Srikanta Dash |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Journal of cancer treatment & diagnosis |
| ISSN: |
2578-2967 |
| Popis: |
Objective The MDR of metastatic breast cancer cells is accompanied by the overexpression of P-gp transporter. This study has been focused to determine whether silencing the expression of P-gp by aptamer-labeled siRNA nanoparticles could enhance the delivery of doxorubicin into breast cancer cells in culture. Methodology The nanoparticle F-31 was prepared using DOTAP, cholesterol, and PLGA, and then incorporating Mal-PEG to facilitate aptamer-binding. The nanoparticles were surface-functionalized with aptamer A6, which targets Her-2 receptors overexpressed on the surface of breast cancer cells. Results This study has shown that the uptake of Dox by Dox-resistant 4T1-R is significantly less than Dox-sensitive 4T1-S which is partly attributed to the higher expression of drug-efflux pump P-gp on the surface of the resistant cells. The targeted knockdown of P-gp has been enhanced when the particles carrying P-gp siRNA was labeled with aptamer. Concurrently, the uptake of Dox into the Dox-resistant 4T1-R breast cancer cells has increased significantly when the P-gp was silenced by P-gp siRNA-encapsulated aptamer-labeled nanoparticles. Conclusions This preliminary study concludes that downregulating P-gp expression by targeted delivery of P-gp siRNA using aptamer-labeled lipid-based hybrid nanoparticles could effectively increase the intracellular trafficking of doxorubicin in Dox-resistant mouse breast cancer cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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