A new study by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) shows that RNA nanoparticles have elastic and rubbery properties that help explain why these particles target tumors so efficiently and why they possess lower toxicity in animal studies.

RNA nanoparticles show great promise for the targeted delivery of anticancer drugs. Understanding their structure and behavior is essential for their possible future use.

This study, published in the journalACS Nano, reveals that RNA nanoparticles have elastic and rubbery properties that enable the molecules to stretch and return to their normal shape. Researchers say that 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 the same 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 relatively quickly. That, in turn, could reduce retention of the anticancer agent in vital organs, lowering an agents 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 authorPeixuan Guo, PhD, professor in the College of Pharmacy and theSylvan G. Frank Endowed Chair in Pharmaceutics and Drug Delivery. Guo is also in the OSUCCC JamesTranslational Therapeutics Research Program.

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 StatesCenter 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 nanoparticle while subjecting RNA nanoparticles to elasticity studies using dual-beam optical tweezers built in Guo Lab. Finally, they used animal models to study the biodistribution, excretion and retention of RNA nanoparticles. This included measuring excretion of the particles in urine along with the study on the effect of their shape and size.

Key findings include:

Overall, Guo says, we believe these findings further support the development of RNA nanoparticles for targeted delivery of anticancer drugs or therapeutic RNA.

Reference: Ghimire C, Wang H, Li H, Vieweger M, Xu C, Guo P.RNA nanoparticles as rubber for compelling vessel extravasation to enhance tumor targeting and for fast renal excretion to reduce toxicity.ACS Nano 2020; doi:10.1021/acsnano.0c04863

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RNA Nanoparticles Rubbery Properties Help Them To Target Tumors - Technology Networks