RNA Nanotechnology Shows Promise for Treating Cancer
A new study by researchers at the University of Kentucky Cancer Nanotechnology Platform Partnership (Kentucky CNPP) shows promise for developing ultrastable RNA nanoparticles that may help treat cancer by regulating cell function and binding to tumors without harming surrounding tissue. This work, led by Peixuan Guo and Mark Evers, was published in the journal Nano Today.
The study uses RNA as a building block for the bottom-up fabrication of nanostructures. The researchers constructed ultrastable X-shaped RNA nanoparticles using re-engineered RNA fragments to carry up to four therapeutic and diagnostic modules. These RNA nanoparticles can include small interfering RNA (siRNA) for silencing genes, micro-RNA (miRNA) for regulating gene expression, RNA aptamers for targeting cancer cells, or RNA-based enzymes, also known as ribozymes, that can catalyze chemical reactions.
In their study, the investigators demonstrated that regulation of cellular functions progressively increased with the increasing number of functional modules in the nanoparticle. “RNA nanotechnology is an emerging field, but the instability and degradation of RNA nanoparticles have made many scientists flinch away from the research in RNA nanotechnology,” Dr. Guo said. “We have addressed these issues, and now it is possible to produce RNA nanoparticles that are highly stable both chemically and thermodynamically in the test tube or in the body with great potential as therapeutic reagents.”
The RNA nanoparticles displayed several favorable attributes: polyvalency, which allows simultaneous delivery of multiple functional molecules for achieving synergistic effects; modular design, which enables controlled self-assembly with defined structure; thermodynamic stability, which keeps the RNA nanoparticles intact in animal and human circulation systems where they exist at very low concentrations; and chemical stability, which makes the nanoparticles resistant to digestion by RNases, enzymes in blood that breakdown RNA.
This work, which is detailed in a paper titled, “Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. The full paper is available at no charge at the journal's website.