'Rubbery' RNA nanoparticles squeeze through tumors for safer delivery of cancer drugs: study

RNA nanoparticles have elastic properties that allow them to stretch and return to their normal shape, a trait that could help them deliver tumor-fighting drugs with fewer side effects, Ohio State University researchers found.

Led by Peixuan Guo, Ph.D., a team at the school’s Comprehensive Cancer Center tested nucleic acid polymers and explored the retention and excretion of RNA nanoparticles in a mouse study published in the journal ACS Nano.

The team’s discovery? RNA nanoparticles have "rubbery" traits that allow them to squeeze through narrow pores and return to their normal shape—“like an amoeba,” Guo said in an interview. That could allow the nanoparticles to breach the poorly formed walls of tumor blood vessels to enter tumor masses and make them a safer drug delivery option for anti-cancer drugs, too, the team posits.

To test the stretchiness of RNA nanoparticles, the team first subjected them to repeated pulling with dual-beam optical tweezers built in Guo’s lab. They discovered that even after undergoing repeated force, the RNA particles snapped back to their original shape, Guo said.

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The team then injected the nanoparticles into mice to test their ability to target tumors and study their retention in the body. They found the RNA nanoparticles displayed stronger cancer-targeting properties and accumulated less in healthy organs than gold and iron nanoparticles, which aren't at all stretchy.

“[The RNA nanoparticles] squeeze themselves up through the tumor blood vessel, under pressure, then get out of the blood vessel and get into the tumor vasculature,” Guo explained. Once those nanoparticles hit the tumor, they’re able to deliver drugs to cancer cells directly, he said. “That’s where the efficacy comes out.”

Meanwhile, those elastic properties could also put a damper on side effects, the researchers figure.

RNA nanoparticles passed through the mouse subjects' kidneys and were excreted in their urine as little as half an hour after injection, the study found. Chemotherapies and other cancer treatments delivered via RNA nanoparticles might accumulate less in vital organs, curbing toxicity overall, the team thinks. 

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The upper limit of kidney pore size is around 5.5-nanometers, Guo explained, but nanoparticles of 5, 10 and even 20 nanometers were able to pass through the kidneys of the mice thanks to their ability to stretch and squeeze through the pores.

That could lead to safer dosing for patients receiving highly toxic cancer treatments, Guo said, because the RNA nanoparticles appear to leave the body still intact after delivering medication to cancer cells.

The team’s revelations about the structure and elasticity of nanoparticles could pave the way for a suite of next-generation cancer treatments, Guo said. Plus, the delivery platform could potentially be used to deploy drugs to the heart and lung.

Meanwhile, Guo has formed a company to tackle RNA nanoparticle delivery. ExonanoRNA, based in Columbus, Ohio, offers RNA nanoparticle services and products to support cancer research. It’s Guo’s hope that the team’s promising discoveries about the mechanical properties of RNA nanoparticles will spark a wave of innovation in the field.