Targeted Delivery of Antisense Oligodeoxynucleotides Formulated in a Novel Lipidic Vector

A novel lipidic system has been developed to selectively deliver oligo-deoxynucleotides (ODN) to target cells. It involves the complexation of ODN with polylysine, followed by the addition of pH-sensitive liposomes that contain a targeting ligand, folate. The resulting particles, named LPDII, efficiently and selectively deliver ODN to human KB cells which overexpress folate-binding proteins (FBP). When an ODN against epidermal growth factor receptors (EGFR) was formulated in LPDII, delivery of these particles to KB cells resulted in down-regulation of EGFR and also cell growth inhibition. Free ODN exhibited no inhibitory effect on the growth of KB cells in the same concentration range. An ODN of scrambled sequence, free or formulated in LPDII, also failed to inhibit the growth of KB cells. Finally, the antisense effect of ODN on KB cells was inhibited by an excess amount of free folate, suggesting that the sequence-dependent effect of the ODN was mediated by folate binding protein.