05 November 2013

Gold nanoparticles and miRNAs against brain cancer

Aggressive brain cancer was slowed down with the help of gold nanoparticles

News from Northwestern University: Incurable Brain Cancer Gene Is SilencedA group of specialists from Northwestern University (Chicago, USA) managed to turn off the gene responsible for the growth and resistance of glioblastoma, the incurable, most aggressive malignant brain tumor.

This result was achieved by the use of spherical nanoparticles with golden cores developed by the authors, delivering small interfering RNAs programmed to reduce oncogene expression to brain cells. The results of the study are published in the journal Science Translational Medicine (Jensen et al., Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma).

The diagnosis of "glioblastoma multiforme" now means a fatal outcome 14-16 months after its diagnosis. The incurable nature of this type of cancer is caused, among other things, by its resistance to chemotherapy due to the difficulty of delivering drugs to the brain, which is separated from the blood by a blood-brain barrier. As a rule, even substances with low molecular weight are not able to overcome this barrier.

At the same time, in recent years, a number of oncogenes have been identified that cause the aggressiveness of glioblastoma and are potential targets of gene therapy, including the Bcl2Like12 gene, whose overexpression in tumor cells and, accordingly, an excess of the protein encoded by this gene supports the growth of glioblastoma.

To solve the problem of delivering gene therapy drugs to tumor cells, the development of the leading author of the work, a specialist in nanomedicine Chad A. Mirkin, made by him back in 1996, spherical nucleic acids (spherical nucleic acids, SNA), was used.

They are tiny spheres, in which gold nanoparticles 13 nanometers in diameter are used as cores. The cores are densely surrounded by small interfering RNAs (siRNAs) – short double-stranded RNAs specially programmed in this case to reduce the expression of Bcl2Like12.

The key in this case is precisely the spherical shape of SNA, as well as their density and very small size. All these parameters allow them to overcome the blood-brain barrier, penetrate into malignant cells and turn off the oncogene.

Experiments on a mouse model of glioblastoma have shown that systemic intravenous administration of SNA leads to a significant decrease in the expression of Bcl2Like12 in glial cancer cells and their apoptosis. The authors noted an almost 20 percent increase in the survival rate of sick animals, and their tumor size decreased three to four times compared to the control group. At the same time, there were no negative side effects of the use of SNA. The next step should be to test this technique in humans.

According to Mirkin, the success of using SNA in vivo can become a platform for gene therapy of a wide range of diseases, from lung and colon cancer, to rheumatoid arthritis and psoriasis.

Portal "Eternal youth" http://vechnayamolodost.ru05.11.2013

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