Intelligent TAT‐coupled anti‐HER2 immunoliposomes knock downed MDR1 to produce chemosensitize phenotype of multidrug resistant carcinoma

• Published in: Journal of cellular physiology Vol. 234; no. 11; pp. 20769 - 20778
• Main Authors: Gholamian Dehkordi, Neda, Elahian, Fatemeh, Khosravian, Pegah, Mirzaei, Seyed Abbas
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2019
• Subjects: Biocompatibility; Cancer; cationic liposome; Cytotoxicity; ErbB-2 protein; Flow cytometry; Gelatinase A; Gene therapy; Gene transfer; Invasiveness; Lipids; Liposomes; MDR1 protein; Monoclonal antibodies; Multidrug resistance; Multidrug resistant organisms; P-Glycoprotein; Phenotypes; Phospholipids; Protein folding; siRNA; Targeted cancer therapy; Transcription; Transfection; Trastuzumab; Tumor cells; multidrug resistance; gene therapy; cancer; cationic liposome; siRNA
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28683

Gene therapy using biocompatible cationic liposomes is amongst promising approaches that decreases death from cancers. Here an invasive multidrug resistant cell model has been developed by lentiviral transfection. In parallel phospholipids have been covalently conjugated to TAT, MMP2, and Herceptin. The functional lipids have been mixed to generate intelligent liposome harboring small interfering RNA (siRNA) with high efficiency. The final liposomal complex was uniformly monodisperse and particle dimension and zeta‐potential were respectively around 200 nm and −42.21 mV. Minimal cytotoxic effects have been reported for nanocarriers due to good biocompatibility of the selected phospholipids. Flourescence‐activated cell sorter (FACS) analyses have been represented that surface trastuzumab and TAT specifically promote cellular uptake of liposomes in the malignant tumor cells. Assessment of MDR1 transcript and protein expression has been exhibited maximum significant downregulation around of 128‐fold and 50‐fold, respectively after 48 hr of liposome exposure. As it has been concluded, targeted liposomes may become a potential tool in gene delivery for improving chemotherapeutic efficiency in cancer treatment. Intelligent liposomes increased cellular uptake of MDR1 small interfering RNA (siRNA) in cancer cells. siRNA delivery significantly downregulated MDR1 gene and protein expression. Downregulation of P‐glycoprotein (P‐gp) increased chemosensitization of cancer cells.