miRNA-filled Nanoparticles for Cancer treatment
The results of the first-of-its-kind clinical studies published on March 21 in the preliminary on-line version of the journal Nature in the article "Evidence of RNAi in humans from systematically administered siRNA via targeted nanoparticles" showed that nanoparticles developed by specialists of the California Institute of Technology, stuffed with small interfering RNAs (miRNAs), effectively penetrate into cancer cells and inhibit the expression of the target gene. The clinical effects of the new therapy have not yet been made public.
The phenomenon of RNA interference (RNAi), which consists in the ability of double-stranded miRNA molecules to block the synthesis of certain proteins, has been considered a promising approach to the development of new drugs for 12 years since its discovery. However, the delivery of therapeutic miRNAs to target cells proved to be a difficult task. After introduction into the body, miRNAs are rapidly excreted by the kidneys, therefore, to ensure their effectiveness, it is necessary to create non-toxic carrier particles capable of delivering their contents to target cells without causing the development of an immune response.
To date, researchers have already conducted several clinical studies in which they tested the ability of miRNA to cure macular degeneration of the retina or infectious lung damage caused by respiratory syncytial virus. These organs are easily accessible for manipulation, so the isolated miRNA was injected directly into the affected tissue. California researchers, working under the guidance of Professor Mark Davis, for the first time carried out the systematic introduction of therapeutic miRNAs enclosed inside specially designed nanoparticles.
The nanoparticles developed by the authors (in the figure – black spheres that can be seen both on the surface and inside the cancer cell) carry a molecular marker that specifically binds to the receptors of the membranes of malignant cells and ensures their penetration into the cells.
miRNA molecules placed in nanoparticles block the synthesis of ribonucleotide reductase M2 (RRM2), an enzyme that controls the repair of DNA damage. The researchers chose this gene as a target (or rather, an informational RNA matrix complementary to it, on which the protein itself is synthesized) in order to increase the likelihood of a positive effect of therapy: overexpression of RRM2 is characteristic of many types of cancer.
Analysis of biopsy samples of malignant tumors – melanomas – of three test participants showed that the concentration of nanoparticles in malignant cells corresponded to the administered dose of the drug. They also isolated samples of mRNAs encoding M2 ribonucleotide reductase from cells and demonstrated that they were altered in the region that the tested miRNAs targeted. The authors did not publish information about the therapeutic effects of the proposed approach, but promised to present all the data they received at the annual congress of the American Community of Clinical Oncologists, which will be held June 4-8 in Chicago. The clinical trials were funded by the recently founded by Davis California company Calando Pharmaceuticals, engaged in the development of cancer treatments using miRNA complexes and nanoparticles.
Experts believe that the work done by the authors is a great achievement, but at the same time emphasize that before their proposed approach is ready for implementation into clinical practice, they still have a lot of work to do.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: RNA-Loaded Nanoparticles Fight Cancer.
23.03.2010