08 November 2016

A double blow to metastases

The bombardment of cancer cells with nanoparticles was tested in vivo

Denis Strigun, Naked Science

American scientists have successfully completed an experiment to remove cancer cells using hydrogel nanoparticles in vivo. The results of the work are published in the journal Scientific Reports (Satpathy et al., Targeted in vivo delivery of EGFR siRNA inhibits ovarian cancer growth and enhances drug sensitivity).

The metastasis (proliferation) of cancer cells may be based on a mutation of the EGFR gene encoding the protein of the same name. As a result, a tumor, such as ovarian cancer, can metastasize into the abdominal cavity, which will significantly complicate treatment and increase the risk of death. At the same time, some metastases are resistant to first–line therapy, in particular tyrosine kinase inhibitors (it "includes" a protein) - cisplastin or carboplatin. This resistance is explained by the fact that cancer cells bind to the glucose cotransporter SGLT1, which provides them with nutrition and prevents death.

Previous studies have shown that the effectiveness of tyrosine kinase inhibitors can be enhanced by hydrogel nanoparticles. So, earlier, researchers from the Georgia Institute of Technology conducted an experiment in which they coated nanoparticles with a synthetic analogue of tyrosine kinase EphA2 and delivered small interfering RNA (miRNA) directly into the tumor with their help. Theoretically, the bombardment of cancer cells with miRNA was supposed to block the synthesis of new proteins in them and stop the growth of the tumor. But until now, the technology has not been tested on living organisms.

In a new experiment, scientists derived a line of cancer cells with increased expression of tyrosine kinase EphA2 and EGFR and injected them into female mice. Thus, metastatic ovarian cancer was simulated in animals. After 18 hours, individuals from the experimental group received four injections of nanoparticles, others were treated with cisplastin or not treated with anything. The results showed that both techniques can slow down the growth of the tumor. At the same time, the effectiveness of cisplastin was more pronounced.

bombing.jpg
Growth of cancer cells in an untreated mouse, after injection of nanoparticles and cisplastin.
A drawing from an article in Scientific Reports.

Then, nine days after cell implantation, one dose of nanoparticles was administered to other individuals from the experimental group and one dose of cisplastin was administered the next day. The analysis showed that the decrease in tumor growth in such mice exceeds the indicators of animals that received only cisplastin or did not receive treatment. At the same time, the greatest decrease in the expression of matrix RNA (mRNA – proteins are synthesized on it) EGFR was observed 24 hours after injection and was restored 72 hours later. The EGFR protein level dropped after 48 hours and did not return to its original level.

Thus, the combination of chemotherapy and a new technique made it possible to significantly reduce or stop the spread of cancer cells in mice. According to scientists, however, clinical trials of nanoparticles will be preceded by a check of their safety and reliability. If approved for human use, the approach can become a tool for the treatment of a wide range of oncological diseases.

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