Make cancer glow
An indicator of dysregulation in living cells is a change in the expression of RNA in them. microRNA (miRNA) is a special type of RNA that is considered a biomarker of atypical (cancer) cells. A group of scientists from China has found a way to amplify miRNA in living cancer cells in order to be able to visualize them. A sufficiently reliable cellular autocatalytic system was used for the analysis a bioscheme triggered by synthetic DNA and nanoparticles.
The diagnosis of a tumor long before the first symptoms appear has been and remains one of the coveted goals of researchers and doctors. One of the biomarkers of malignancy in a cell is the nature of RNA expression or, more precisely, a change in RNA expression that causes metabolic degeneration. There are many types of RNA, including a short non-coding miRNA, which promotes or prevents the translation of genetic information into a protein. Accordingly, the detection of an altered miRNA expression profile is considered a reliable indicator of cell degeneration.
But the detection of a specific miRNA was previously difficult: it is present in the cell in small quantities, so it must be amplified and connected to a signaling object, such as a fluorescent dye, for visualization.
A group of researchers from Wuhan University in China, led by Fuan Wang, has selected a suitable mechanism for amplification and detection of miRNA, which is based on an autocatalytic bioscheme activated by synthetic DNA and leads to a fluorescent signal that marks tumor cells.
RNA is usually synthesized in the cell nucleus and transported to the cytoplasm, where it transmits genetic information. But when synthetic DNA is present in the cytoplasm, RNA can bind to the corresponding nucleotide sequence of the DNA chain. This property is used, for example, in antiretroviral treatment to suppress the expression of viral RNA. Wang and his colleagues did the opposite. By matching strands of synthetic DNA with miRNA, they launched an autocatalytic amplification scheme – the so–called autocatalytic bioscheme DNKzima - to form DNA/miRNA assemblies. These assemblies increase and form DNKZIM nanofibers that carry fluorescent dyes.
After the introduction of the kit for the determination of DNKZIM, the authors observed bright fluorescence on a mouse model in the place where the tumor developed.
Source: article in Angewandte Chemie.
To force DNKzim to penetrate tumor cells, the authors used nanoparticles made of manganese dioxide with a cellular structure. According to the authors, this composition and architecture allow nanoparticles to be easily activated by the action of glutathione, which is abundant in cancer cells. Another advantage is that the released manganese ions support the autocatalytic bioscheme of DNKZIM.
Scientists emphasize that their self-reinforcing system can be used as a powerful tool for imaging tumor cells using biomarkers. It is especially important that miRNAs can be selectively selected for various types of cancer or other cellular dysfunction.
Article J.Wei et al. A Smart, Autocatalytic, DNAzyme Biocircuit for in Vivo, Amplified, microRNA Imaging is published in the journal Angewandte Chemie.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Wiley Online Library: Amplification and imaging of microRNA as a biomarker to detect tumor development.