Poster abstracts

Poster number 21 submitted by Peixuan Guo

The Hydrophobic Effect from conjugated chemicals or drugs on in Vivo Biodistribution of RNA Nanoparticles

Daniel L. Jasinski (College of Pharmacy and College of Medicine, The Ohio State University), Hongran Yin (College of Pharmacy and College of Medicine, The Ohio State University), Zhefeng Li (College of Pharmacy and College of Medicine, The Ohio State University), Peixuan Guo (Collge of Pharmacy and College of Medicine, The Ohio State University)

Abstract:
In vivo liver or other organ accumulation of drugs is one of the major problems that leads to toxicity and side effects in therapy using chemicals or other macromolecules. It has been shown that specially designed RNA nanoparticles can specifically target cancer cells, silence oncogenic genes, and stop cancer growth with little or no accumulation in the liver or other vital organs. It is well known that physical properties of nanoparticles such as size, shape, and surface chemistry affect biodistribution and pharmacokinetic profiles in vivo. In this study, we examined how the hydrophobicity of chemicals conjugated to RNA nanoparticles affect in vivo biodistribution. Weaker organ accumulation was observed for hydrophobic chemicals after they were conjugated into RNA nanoparticles, suggesting that RNA nanoparticles have the property to increase the solubility of hydrophobic chemicals. We found that different chemicals conjugated to RNA nanoparticles resulted in the alternation of RNA hydrophobicity. The stronger hydrophobicity induced by chemical conjugates resulted in higher accumulation of RNA nanoparticles in vital organs in mice. This study offer insight into drug development concerning the reduction of organ accumulation and drug toxicity or side effects.

References:
1. Guo P. The emerging field of RNA nanotechnology. Nature Nanotechnology. 2010. 5:833-42.
2. Shu D, Shu Y, Haque F, Guo P. Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nature Nanotechnology. 2011. 6:658-67.

Keywords: RNA nanoparticles, pRNA 3WJ motif, Biodistribution