(324b) Targeted PEGylated Liposomes for DNA Delivery Specific to α5β1 Bearing Cancer Cells

We devised a PR_b targeted stealth liposomal vesicle encapsulating condensed plasmid DNA to specifically deliver the payload to cancer cells bearing the α₅β₁ integrin. PR_b is a fibronectin mimetic peptide previously developed within our group and shown to outperform both GRGDSP and fibronectin in in vitro cell binding experiments.  In the present study, we have combined the DNA packaging and intracellular release properties of cationic polymers with the protective and targeting properties of our PR_b targeted PEGylated liposomes to formulate an efficient gene delivery vehicle. We demonstrate the in vitro targeting properties of PR_b targeted stealth liposomes with CT26 colon cancer cells expressing α₅β₁ integrin. Moreover we emphasize the importance of targeting specificity in the formulation of an efficient delivery system. To this end, we demonstrate the better specificity of DNA encapsulated PR_b targeted liposomes compared to other common gene delivery systems including widely used polyplexes with in vitro experiments transfecting CT26 cells and with in vivo biodistribution experiments in tumor bearing mice models.