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Cancer Stem Cell-Targeted Gene Delivery Mediated by Aptamer-Decorated pH-Sensitive Nanoliposomes
Parikshit Moitra1,2, Santosh K Misra3, Krishan Kumar3
1Department of Pediatrics, Center for Blood Oxygen Transport and Hemostasis, School of Medicine, Health Sciences Facility III, University of Maryland Baltimore, 670 W Baltimore Street, Baltimore, Maryland 21201, United States.
Abstract:
A new pH-responsive cationic co-liposomal formulation was prepared in this study using the twin version of the amphiphile palmitoyl homocysteine, TPHC; natural zwitterionic lipid, DOPE; and cholesterol-based twin cationic lipid, C5C, at specified molar ratios. This co-liposome was further decorated with a newly designed fluorescently tagged, cholesterol-tethered EpCAM-targeting RNA aptamer for targeted gene delivery. This aptamer-guided nanoliposomal formulation, C5C/DOPE/TPHC at 8:24:1 molar ratio, could efficiently transport the genes in response to low pH of cellular endosomes selectively to the EpCAM overexpressing cancer stem cells. This particular observation was extended using siRNA against GFP to validate their transfection capabilities in response to EpCAM expression. Overall, the aptamer-guided nanoliposomal formulation was found to be an excellent transfectant for in vitro siRNA gene delivery.
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