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RNA Nanoparticles Advanced for Cancer Drug Delivery

Peixuan Guo (University of Kentucky)

Peixuan Guo (University of Kentucky)

Medical researchers at University of Kentucky and University of Nebraska developed nanoscale particles using RNA to deliver cancer drugs that could bind to and regulate cells in mice without harming other tissue. The results of the research carried out in the the lab of Kentucky’s Peixuan Guo (pictured right) appear in the August issue of the journal Nano Today.

Guo’s team built the nanoscale drug delivery system around ribonucleic acid or RNA, a derivative of DNA, with four separate modules:

– Interference RNA for silencing genes
– Micro-RNA for regulating gene expression
– An aptamer, RNA molecules with the ability to bind other molecules, for targeting cancer cells
– Ribonucleic acid enzyme or ribozyme, an RNA molecule that can catalyze a chemical reaction

The researchers fabricated these features into X-shaped nanoparticles using re-engineered RNA fragments. The construction made the nanoparticles modular, with each arm of the X holding a separate component. The team tested the nanoparticles on mice with cancer and found the nanoparticles could increase their potency by increasing the amount of gene-silencing interference RNA.

The instability of RNA, notes Guo, has been a barrier that up to now has discouraged research into RNA-based therapies. “RNA nanotechnology is an emerging field,” says Guo, “but the instability and degradation of RNA nanoparticles have made many scientists flinch away from the research in RNA nanotechnology.”

The tests on mice indicate the Kentucky RNA nanoparticles could clear those barriers. The results show the nanoparticles are thermodynamically stable, which keeps the RNA nanoparticles intact in animal and human circulation systems in low concentrations. The tests also show the nanoparticles were chemically stable, resisting digestion from blood enzymes that can alter the chemistry of RNA.

The findings show as well that that the RNA nanoparticles target the cancer and not other types of tissue in the mice. The tests indicate that the RNA particles remain intact and bind strongly to cancers and remain in cancer tissue for more than eight hours, without entering the liver, lung or any other organs or tissues.

Co-author Mark Evers of Kentucky’s Markey Cancer Center says, “Using the nanotechnology approach that Peixuan Guo and his group have devised may allow us to more effectively treat cancer metastasis with fewer side effects compared to current chemotherapy.”

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