Targeted Delivery of Antisense Oligodeoxynucleotides by LPDII

Successful application of oligodeoxynucleotides (ODNs) to disease treatment requires the development of a suitable vector. Current vectors suffer from one or more of the following problems: low incorporation efficiency, poor cellular uptake, inefficient cytoplasmic release and lack of cell type specificity. We describe here a novel formulation, LPDII, which might avoid above problems. ODNs are first complexed with polylysine (PLK) and then coated with negatively charged liposomes composed of dioleoylphosphatidylethanolamine (DOPE)/cholesteryl hemisuccinate (CHEMS)/folate-poly (ethylene glycol) (PEG)-DOPE to form LPDII particles carrying a targeting ligand, folate. The LPDII could be specifically recognized by KB cells which overexpress folate binding protein. Delivery of an antisense ODN against epidermal growth factor receptor (EGFR) resulted in down-regulation of EGFR and growth inhibition of KB cells. The delivery of ODNs by LPDII was more efficient than folate-targeted liposomes containing phosphatidylcholine (PC)/cholesterol/folate-PEG-DOPE.