In a tumor on a ride
Biologists have turned the "cousin" of egg white into a "killer" of cancer cells
Albumin protein molecules, a human analog of chicken egg protein, can be used to deliver specific genetic signals to cancer cells that cause them to kill themselves or stop their reproduction, according to an article published in the journal PNAS (Sarett et al., Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing).
"We used albumin for the reason that it is the most common protein in human blood. Our RNA molecules can attach to a special "fat pocket" inside albumin, which allows them to live for several days in the bloodstream, and not disappear from the body after two minutes when they reach the kidneys," explains Craig Duvall from Vanderbilt University in Nashville (USA).
As scientists explain, RNA plays the role of the main information carrier in living cells – it "conducts" the activity of genes and how actively they are read. Molecular biologists are actively trying to take advantage of this property of RNA today, using short RNA molecules to create living "biocomputers" based on microbes, as well as drugs that suppress the work of genes in microbes or trigger the process of self-destruction of cancerous tumors.
The first attempts to carry out such an operation in a living organism, as Duvall recalls, ended in failure – "naked" RNA molecules were destroyed by the immunity of experimental animals faster than they could penetrate cancer cells. When scientists "wrapped" these molecules in nanoparticles, they stopped breaking down quickly, but still did not get into the tumor, as they began to accumulate in the liver.
This forced Duvall and his colleagues to look for fundamentally different ways of delivering short RNAs to cancer cells that would not lead to the rapid destruction or withdrawal of "killer" molecules from the body.
Scientists have noticed two things: that cancer cells absorb noticeably more nutrients from the external environment, and that albumin molecules, one of the key proteins of the blood, penetrate them quite often.
As Duvall notes, albumin molecules contain special "pockets" inside which the protein usually carries various fats and other long molecules, moving them from the bloodstream to the cell and back. These "pockets", as scientists have suggested, may be large enough to carry in themselves and short RNAs, "posing" as fat molecules and similar to them in shape.
To test this approach to cancer treatment, scientists obtained several fragments of a tumor extracted from the breast, some of which they treated with "ordinary" nanoparticles, and others with a mixture of RNA and albumin.
As experiments have shown, albumin and RNA penetrated into all cancer cells, correctly "unpacked" and turned off those genes that cause cancer cells to multiply uncontrollably. Nanoparticles were able to suppress these genes in only 60% of cells, so that the tumor did not lose the ability to resist therapy and grow further. In general, RNA particles in an albumin "package" acted on the tumor three times more strongly than RNA in combination with nanoparticles.
Figure from the press release Hijacking human proteins to better deliver anti-cancer drugs - VM.
"The most amazing thing about this approach is that it not only improves the penetration of RNA molecules into the tumor, but at the same time is absolutely non-toxic even at very high doses. This makes it possible to use a similar delivery system to block many genes, which is necessary to fight tumors that are able to adapt to such procedures," concludes Dana Brantley–Sieders, Duvall's colleague at the university.
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25.07.2017