(267b) Delivery of HIF1a siRNA for Atherosclerosis Plaques Using Targeted Polyelectrolyte Complex Micelles
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Materials Engineering and Sciences Division
Polymer Thermodynamics and Self-Assembly: In Solution
Tuesday, November 17, 2020 - 8:15am to 8:30am
Our strategy is to encapsulate HIF1α siRNA with targeting peptide-PEG (polyethylene glycol)-PLK (polylysine) molecules. This results in the formation of electrostatically driven, self-assembled micelles with a polylysine-siRNA core, protected by a PEG corona that is decorated with the targeting peptide. The formation of siRNA-containing, peptide-targeted micelles is achieved via electrostatic complexation between the negatively charged siRNA and positively charged polycations containing targeting peptides. Polycation molecule contains three functional domains, which are targeting peptides for cellular or plaque localization, a polyethylene glycol domain to prevent macrophase separation, and a polylysine domain to complex with the negatively charged siRNA. The targeting peptide has the sequence valine-histidine-proline-lysine-glycine-histidine-arginine, or VHPKQHR, which are enabled for targeting VCAM-1 on the surface of endothelial cells. By taking advantage of the benefits of self-assembly, we can tailor the micelle corona to enable the targeting of diverse cell types and load the micelles with specific siRNA, thereby providing the means to target various pathological mechanisms in a wide range of cells and contexts.