Poster abstracts
Poster number 25 submitted by Daniel Jasinski
The Effect of Size and Shape of RNA Nanoparticle on Biodistribution
Daniel L. Jasinski (College of Pharmacy and College of Medicine, The Ohio State University), Hui Li (College of Pharmacy and College of Medicine, The Ohio State University), Peixuan Guo (College of Pharmacy and College of Medicine, The Ohio State University)
Abstract:
In vivo liver or other organ accumulation of drugs or nanoparticles is a hurdle in therapeutics due to the consequence of toxicity and side effects. The mechanism of organ accumulation has been extensively investigated, and it has been reported that the accumulation is size-dependent and in large part due to engulfing of nanoparticles by macrophages such as the Kupffer cell in livers. However, findings in literature about the effect of size on organ accumulation are inconsistent due to the complication by the effect of shape, which varies from nanoparticle to nanoparticles. RNA nanoparticles are tunable in size and shape, making them an ideal system to study how these factors affect in vivo delivery properties such as circulation time and biodistribution. Unique to RNA nanoparticles, size could be studied without change in shape, resulting in a true comparison of size effect on pharmacokinetics and biodistribution. In this study, we constructed RNA triangles, squares, and pentagons that display different size. The effect of particles size and shape in relation to biodistribution is investigated using the RNA polygons with variable size but identical shape, and with variable shape but identical size. It was found that increasing the size of the nanoparticles increased circulation time, while still avoiding significant entrapment in the liver and kidneys. Difference in shape appeared to have no effect on final biodistribution, however, evidence points towards diverse routs of clearance among different RNA polygons. Despite increasing size, we still see little accumulation in the liver, kidneys, and spleen after 24 h of circulation with particle with 5-25 nanometers.
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 Nanotechnology, biodistribution, size and shape effects