590. Tumor-Targeted Delivery of Therapeutic siRNA by EGFR Aptamer-Conjugated Liposomes

Abstract

Important considerations for effective cancer gene therapy are the targeted delivery of therapeutic genes and efficient endosomal escape of the genes in the cytoplasm. To address the first issues, target-specific aptamers and cationic lipids have been adopted for formulation of tumor-specific lipidic nanoparticles containing therapeutic genes. First of all we have developed EGF receptor (EGFR) aptamer-conjugated liposomes containing siRNA. The liposomal vehicles were optimized in terms of lipid constituents, ratio of lipid/siRNA, and aptamer conjugation process, and their biophysical characteristics were then determined by dynamic light scattering. Compared to the nonspecific cationic lipoplexes of siRNA, EGFR aptamer-conjugated liposomes encapsulating siRNA showed a relatively lower binding to EGFR-expressing cancer cells, resulting in a lower siRNA transfection. However, the EGFR aptamer-conjugated liposomes exhibited efficient transfection only to EGFR-expressing cancer cells, but not to EGFR-negative cancer cells. This research suggests that aptamer-conjugated lipidic nanoparticles can be utilized for target-specific delivery of therapeutic siRNAs.