2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

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TechConnect Summit
Clean Technology 2008

Organisation of peptide ligands on the surface of gene vectors

M. Wang, A.D. Miller, M. Thanou
Imperial College London, UK

gene delivery, targeting, cancer, peptide, liposome

Through the considerate organisation of surface ligands, we have developed a lipid-based vector for the targeted delivery to cancer cells. Our ligand is a short peptide with high affinity for the Urokinase Plasminogen Activator receptor (uPAR), a receptor overexpressed on the surface of many tumours. We modified the surface of a high-charge liposomal vector with uPAR-specific peptides, by inserting peptide-lipid conjugates onto the surface of preformed lipoplexes. Transfections on uPAR-overexpressed cell lines showed increase in protein expression by targeted-vectors compared to non-modified vectors. The selectivity of the uPAR-specific peptide was verified by the decrease in transfection levels by vectors modified with a scrambled peptide sequence non-specific to uPAR. On lowering the zetapotential of the liposomal platform, non-specific interactions with the cell membranes were reduced, resulting in a further increase in transfection efficiency by targeted vectors. FACS studies and fluorescent microscopy suggest that the targeted vectors improve the binding and uptake by cancer cells. Conjugation of the peptide onto the distal end of PEG chains within the low-charge vector surface resulted in an even further increase of transfection efficiency. We conclude that the nature of the liposomal platform (stability, zetapotential) with the presentation of surface ligands, contribute to the maximisation of a vector’s targeting effect.

Nanotech 2008 Conference Program Abstract