Structure-Property Relationships of Polyelectrolyte Complex Micelles for Targeted Delivery of RNA to Atherosclerotic Plaques

Polyelectrolyte complex (PEC) micelles are of immense therapeutic interest because of their ability to encapsulate nucleic acid and protect it from degradation. Formed by mixing the nucleic acid with a block copolymer of one neutral hydrophilic block and one charged block, the micelles can be injected as therapeutic agents to deliver the nucleic acid to an area of interest. PEC micelles are highly versatile, as a targeting moiety can be attached to the block copolymer modularly, allowing for a wide range of potential targets for the encased nucleic acid. To take advantage of this potential for modular design, and to understand the dynamics of the micelles in vivo, it is important to understand the fundamental structural properties of the micelles: their shape, size, and internal structure. Using small-angle X-ray scattering (SAXS) and light scattering, we can observe and characterize these properties in PEC micelles, and compare micelles of different assembly inputs such as nucleic acid structure, charged block length, neutral block length, salinity of solution, and charge of targeting moiety. Therefore, we can elucidate what properties influence the shape, size, and internal structure of the micelles. Then, I demonstrate that these micelles are an effective RNA delivery vehicle for the treatment of atherosclerosis, a chronic cardiovascular disease.