155. Cancer-Specific Theranosis Using Quantum Dots and siRNA Co-Loaded in Micellar Nanoparticles

Abstract

Theranostics is a proposed process of diagnostic therapy for an individual patient. It has been considered a powerful tool of personalized medicine. In this study, we have prepared lipid micellar nanoparticles encapsulating quantum dots (QDs) as a diagnostic agent and incorporating cholesterol-siRNA (Cho-siRNA) as a therapeutic agent. Furthermore, for targeted delivery of QDs and Cho-siRNA, anti-EGFR antibodies or aptamers were conjugated to the surface of the nanoparticles. First of all, for stable nanostructure of lipid micelles, we determined an optimal molar ratio of lipids, QDs, and Cho-siRNA as 350:1:0.35. The size of QD micelles was approximately 50 nm that is suitable for efficient localization in tumors via enhanced permeability and retention (EPR) effect. Their serum stability and pH stability suggest that the QD micelle structure is stable enough to be applied under biological conditions. The RNase protection assay showed that Cho-siRNA molecules in the QD micelles were effectively protected by steric shielding of hydrophilic polyethylene glycol molecules. The analyses with a flow cytometry and a confocal microscope showed that the nanoparticles can effectively deliver Cho-siRNA to the target cells, followed by effective residing of siRNA molecules in the cytoplasm. A further systematic evaluation of the micellar nanoparticles established in this study would verify their value as a theranostic vehicle.