Poster abstracts

Poster number 129 submitted by Congcong Xu

Favorable Biodistribution, Specific Targeting and Conditional Endosomal Escape of RNA Nanoparticles in Cancer Therapy

Congcong Xu (College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, Ohio, USA), Farzin Haque (Nanobio Delivery Pharmaceutical Co. Ltd., Columbus, OH, USA), Daniel L. Jasinski (College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, Ohio, USA), Daniel W. Binzel (College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, Ohio, USA), Dan Shu (College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, Ohio, USA), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; College of Medicine, Dorothy M. Davis Heart and Lung Research Institute )

Abstract:
The past decades have witnessed the success transition of several nanotechnologies into the clinic. However, specific delivery of therapeutics to tumors is hindered by several barriers including cancer recognition and tissue penetration; particle heterogeneity and aggregation; unfavorable pharmacokinetic profiles such as fast clearance and organ accumulation. With the advent of RNA nanotechnology, a series of RNA nanoparticles have been successfully constructed to overcome many of the aforementioned challenges for in vivo cancer targeting with favorable biodistribution profiles. Compared to other nanodelivery platforms, the physiochemical properties of RNA nanoparticles can be tuned with relative ease for investigating the in vivo behavior of nanoparticles upon systemic injection. The size, shape, and surface chemistry, especially hydrophobic modifications, exert significant impacts on the in vivo fate of RNA nanoparticles. Rationally designed RNA nanoparticles with defined stoichiometry and high homogeneity have been demonstrated to specifically target tumor cells while avoiding accumulation in healthy vital organs after systemic injection. RNA nanoparticles can deliver therapeutics such as siRNA and anti-miRNA to block tumor growth in several animal models. Although the release of anti-miRNA from the RNA nanoparticles has achieved high efficiency of tumor regression in multiple animal models, the efficiency of endosomal escape for siRNA delivery needs further improvement. This presentation will focus on the advances and perspectives of this promising RNA nanotechnology platform for cancer targeting and therapy.

References:
[1] P. Guo, The emerging field of RNA nanotechnology. Nature Nanotechnology 5 (2010) 833-842.
[2] D. Shu, Y. Shu, F. Haque, S. Abdelmawla, and P. Guo, Thermodynamically stable RNA three-way junctions for constructing multifuntional nanoparticles for delivery of therapeutics. Nature Nanotechnology 6 (2011) 658-667.
[3] D. Jasinski, F. Haque, D.W. Binzel, and P. Guo, Advancement of the Emerging Field of RNA Nanotechnology. ACS Nano 11 (2017) 1142-1164.
[4] Y. Shu, F. Haque, D. Shu, W. Li, Z. Zhu, M. Kotb, Y. Lyubchenko, and P. Guo, Fabrication of 14 Different RNA Nanoparticles for Specific Tumor Targeting without Accumulation in Normal Organs. RNA 19 (2013) 766-777.
[5] H. Li, K. Zhang, F. Pi, S. Guo, L. Shlyakhtenko, W. Chiu, D. Shu, and P. Guo, Controllable Self-Assembly of RNA Tetrahedrons with Precise Shape and Size for Cancer Targeting. Adv. Mater. 28 (2016) 7501-7507.

Keywords: RNA nanotechnology, pRNA-3WJ, Biodistribution