RNA nanoparticles show promise for the targeted delivery of anticancer drugs; understanding their structure and behavior is essential for their future use. This study, published in the journal ACS Nano, reveals that RNA nanoparticles’ elastic and rubbery properties enable them to stretch and return to their normal shape. Researchers say these properties could help the particles target tumors by enabling them to slip through the poorly formed walls of tumor blood vessels and enter a tumor mass.
The researchers further proved that those rubbery properties enable the RNA nanoparticle to slip through the kidney to excrete into the urine a half-hour after systemic injection, thereby eliminating them from the body. That, in turn, could reduce retention of the anticancer agent in vital organs and lower the agent’s toxicity.
“We show that RNA nanoparticles have a flexibility that allows for the assembly of molecular structures that have stretchable angles,” says study leader and corresponding author Peixuan Guo, PhD, a professor in the College of Pharmacy and the Sylvan G. Frank Endowed Chair in Pharmaceutics and Drug Delivery. Guo is also in the Translational Therapeutics Program at the OSUCCC – James.
“These findings demonstrate the rubbery properties of RNA nanoparticles and why these molecules hold great promise for industrial and biomedical applications, especially as carriers for targeted delivery of anticancer drugs,” says Guo, who directs Ohio State’s Center for RNA Nanobiotechnology and Nanomedicine.
For this study, Guo and his colleagues tested the elasticity of nucleic acid polymers by stretching and relaxing individual RNA nanoparticles while subjecting them to elasticity studies using dual-beam optical tweezers built in the Guo lab. They then used animal models to study the biodistribution, excretion and retention of RNA nanoparticles. This included measuring excretion of the particles in urine and studying the effect of their shape and size.
“Overall,” Guo says, “we believe these findings further support the development of RNA nanoparticles for targeted delivery of anticancer drugs or therapeutic RNA.”