(109f) Dual-Ligand Peptide-Targeted Liposomal Gene Delivery for Cancer Therapy

Gene therapy is a powerful tool with the potential to fight cancer at the genetic level, however, effective delivery of gene therapy is a great obstacle to the clinical application of cancer gene therapy.  DNA encapsulating stealth liposomes specifically targeted to cancer tissue with peptide ligands have the potential to overcome this obstacle. Moreover, dual peptide targeting can be utilized to improve both the binding efficency and specificity of delivery vehicles.  In this work, a reliable DNA quantification method and optimal production conditions were developed and analyzed for DNA encapsulated stealth liposomes.  Stealth liposomes were then functionalized with two peptide ligands to explore the effect of dual targeting on liposome binding to cancer cells.  Dual targeting was shown to improve binding compared to single targeting with stealth liposomes in vitro. Several peptide concentrations and ratios were evaluated to understand the effect of ligand valency on cell binding.  The optimal dual targeted stealth liposome formulation was used to deliver gene therapy showing enhanced toxicity to cancer cells compared to healthy cells in vitro.