Poster abstracts
Poster number 61 submitted by Hongran Yin
RNA-based micelles: A novel platform for paclitaxel loading and delivery
Hongran Yin (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; The Ohio State University, Columbus, OH 43210, United States), Yi Shu (Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, United States), Mehdi Rajabi, Hui Li (Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, United States), Mario Vieweger (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; The Ohio State University, Columbus, OH 43210, United States), Sijin Guo (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; The Ohio State University, Columbus, OH 43210, United States)
Abstract:
RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures for biotechnological and biomedical applications. In addition to current self-assembly strategies utilizing base pairing, motif piling and tertiary interactions, we reported for the first time to build RNA based micellar nanoconstruct with a cholesterol molecule conjugated onto one helical end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic RNA micelles consist of a hydrophilic RNA head and a covalently linked hydrophobic lipid tail that can spontaneously assemble in aqueous solution via hydrophobic interaction. Taking advantage of the feature of pRNA 3WJ branched structure, the assembled RNA micelles are capable of escorting multiple functional modules. As a proof of concept for delivery for therapeutics, Paclitaxel was loaded into the RNA micelles with significantly improved water solubility. The successful construction of the drug loaded RNA micelles was confirmed and characterized by agarose gel electrophoresis, atomic force microscopy (AFM), dynamic light scattering (DLS), and fluorescence Nile Red encapsulation assay. The estimate critical micelle formation concentration ranges from 39nM to 78nM. The Paclitaxel loaded RNA micelles can internalize into cancer cells and inhibit their proliferation. Further studies showed that the Paclitaxel loaded RNA micelles induced cancer cell apoptosis in a Caspase-3 dependent manner but RNA micelles alone exhibited low cytotoxicity. Finally, the Paclitaxel loaded RNA micelles targeted to tumor in vivo without accumulation in healthy tissues and organs. There is also no or very low induction of pro-inflammatory response. Therefore, multivalence, cancer cell permeability, combined with controllable assembly, low or nontoxicity nature, and tumor targeting are all promising features that make our pRNA micelles a suitable platform for potential drug delivery.
Keywords: pRNA three way junction, RNA nanotechnology, RNA micelles