Vol 4-1 Original Research Article

Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein

Sruti Chandra1, Hoang Michael Nguyen1, Kylar Wiltz1, Nicholas Hall1, Shanzay Chaudhry1, George Olverson1, Tarun Mandal2, Srikanta Dash3, Anup Kundu1*

1Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana

2Center for Nanomedicine and Drug Delivery, Xavier University College of Pharmacy, New Orleans, Louisiana

3Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana

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.

DOI: 10.29245/2578-2967/2020/1.1176 View / Download Pdf