MOSCOW, May 17, 2021 /PRNewswire/ — A Russian-German research team has come up with a new technique for magnetic resonance imaging of cancer cells. The study, published in Pharmaceutics, shows that heterologous expression of encapsulin systems from Quasibacillus thermotolerans with functional cargo proteins and iron transporter leads to increased contrast in MRI imaging of mammalian tumor cells.
Currently, the primary method of live-cell imaging is direct labeling of cells with a probe or contrast agent before transplantation. However, any synthetic contrast agent for cell labeling has a critical drawback — it dilutes as the cells divide, which leads to loss of the signal after several cycles of divisions. In contrast, genetically encoded reporters propagate to daughter cells with each cell division. Moreover, their signal is selective for viable cells.
Ferritin, a blood protein that contains iron, is the most studied genetically encoded agent so far. However, ferritin’s MRI performance is limited by its weak magnetic properties and highly conservative structure.
«One of the most promising approaches is based on the heterologous expression of bacterial protein nanocompartments — encapsulins — in mammalian cells. Encapsulins can serve as genetically controlled labels for multimodal detection of cells. They can host various guest molecules inside their lumen. These include, for example, fluorescent proteins or enzymes with ferroxidase activity,» says Maxim Abakumov, head of the NUST MISIS Biomedical Nanomaterials Laboratory, senior researcher at the Medicinal Nanobiotechnology Department, N.I. Pirogov Russian National Research Medical University.
A team of scientists from NUST MISIS, V. Serbsky National Medical, N.I. Pirogov Russian National Research Medical University, Technical University of Munich, Helmholtz Center Munich have implemented, for the first time, heterologous expression of encapsulin systems from Quasibacillus thermotolerans using a fluorescent reporter protein and ferroxidase in human hepatocellular carcinoma cells. Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA. The researchers loaded the nanoshell with the natural ferroxidase cargo from Q. thermotolerans and a synthetic fluorescent cargo protein derived from mScarlet-I. The successful expression of self-assembled encapsulin nanocompartments with functional cargo proteins was then confirmed by fluorescence microscopy and transmission electron microscopy. Also, coexpression of encapsulin nanoshells, ferroxidase cargo, and iron transporter led to an increase in contrast in magnetic resonance imaging of cancer cells.
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SOURCE The National University of Science and Technology MISiS