Fatty Acid Synthase (FASN) siRNA-Encapsulated-Her-2 Targeted Fab’-Immunoliposomes for Gene Silencing in Breast Cancer Cells

Abstract

Arif Khan,1,* Ahmed N Aljarbou,2 Yousef H Aldebasi,3 Khaled S Allemailem,4 Mohammed A Alsahli,1 Shamshir Khan,5 Abdulmohsen M Alruwetei,4 Masood A Khan1,* 1Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Al-Qassim, Buraydah, Saudi Arabia; 2Department of Pharmaceutics, College of Pharmacy, Qassim University, Al-Qassim, Buraydah, Saudi Arabia; 3Department of Optometry, College of Applied Medical Sciences, Qassim University, Al-Qassim, Buraydah, Saudi Arabia; 4Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Al-Qassim, Buraydah, Saudi Arabia; 5Dentistry and Pharmacy College, Buraydah Private Colleges, Al-Qassim, Buraydah, Saudi Arabia*These authors contributed equally to this workCorrespondence: Arif Khan; Masood A KhanDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi ArabiaEmail [email protected]; [email protected]: The overexpression of Her-2 in 25– 30% breast cancer cases and the crosstalk between Her-2 and fatty acid synthase (FASN) establishes Her-2 as a promising target for site-directed delivery. The present study aimed to develop the novel lipid base formulations to target and inhibit the cellular proliferation of Her-2-expressing breast cancer cells through the silencing of FASN. In order to achieve this goal, we prepared DSPC/Chol and DOPE/CHEMS immunoliposomes, conjugated with the anti-Her-2 fab’ and encapsulated FASN siRNA against breast cancer cells.Methods: We evaluated the size, stability, cellular uptake and internalization of various formulations of liposomes. The antiproliferative gene silencing potential was investigated by the cell cytotoxicity, crystal violet, wound healing and Western blot analyses in Her-2+ and Her-2® breast cancer cells.Results: The data revealed that both nanosized FASN-siRNA-encapsulated liposomes showed significantly higher cellular uptake and internalization with enhanced stability. The cell viability of Her-2+ SK-BR3 cells treated with the targeted formulation of DSPC/Chol- and DOPE/CHEMS-encapsulating FASN-siRNA reduced to 30% and 20%, respectively, whereas it was found to be 45% and 36% in MCF-7 cells. The wounds were not only failed to close but they became broader in Her-2+ cells treated with targeted liposomes of siRNA. Consequently, the amount of FASN decreased by 80% in SK-BR3 cells treated with non-targeted liposomes and it was 30% and 60% in the MCF-7 cells treated with DSPC/Chol and DOPE/CHEMS liposomes, respectively.Conclusion: In this study, we developed the formulation that targeted Her-2 for the suppression of FASN and, therefore, inhibited the proliferation of breast cancer cells.Keywords: gene therapy, pH-sensitive liposomes, DRVs, stealth pegylated

Keywords

• gene therapy
• ph-sensitive liposomes
• drvs
• stealth pegylated