Nanobombs against metastases

Filled with poison nanosheets destroyed metastases in mice

Evgenia Efimova, Vesti

The greatest risk for most patients with cancer is not so much the disease itself as metastases. They are like the tentacles of an octopus spreading from the tumor site in different directions, from one organ to another. So metastases can penetrate into the lungs, liver and various tissues.

But scientists from the USA have come up with a method to combat metastases with the help of "poison" (First injectable nanoparticle generator could radically transform metastatic breast cancer treatment).

The treatment is carried out in three steps, during which the substance used in chemotherapy today is gradually placed in close proximity to the nucleus of a metastatic cancer cell. Only in this case, the drug molecules are the most deadly for cells.

"It's almost like a multi-stage rocket" that lifts astronauts into space, sends them to the moon and then returns them back, Stephen Libutti, a geneticist and oncologist surgeon from the Albert Einstein College of Medicine, draws an analogy.

The new therapy is based on a chemotherapeutic substance called doxorubicin – an anthracycline antibiotic. Such a substance is obtained from bacteria of the species Strcptomyccs pcucctius cacsius, and it is used mainly for the treatment of various types of malignant tumors. Doxorubicin acts on the DNA of tumor cells, preventing their further division.

However, there is one important "but": when it is injected into the circulatory system, such a drug can also kill the heart muscle or lead to heart failure. Such an adverse effect, in turn, often forces oncologists to reduce the dose, or stop using doxorubicin altogether.

It is highly desirable to deliver such an antibiotic only to tumor cells, but it is difficult to do this.

A team of researchers led by Mauro Ferrari, a nanomedical expert and head of the Houston Methodist Research Institute in Texas, spent years developing a special porous silicon particle that would become a "carrier" of the drug.

The micron size and disc-shaped shape of the particle allow it to pass freely through healthy blood vessels. But when they get into the vessels near the tumor, which are usually deformed, the particles leave the circulation and end up next to the tumor.

This was the first stage in delivering a chemotherapeutic drug to its target. But simply filling such particles with doxorubicin will not do much good, Ferrari believes.

Even if a small amount of the drug gets inside the tumor cells, their proteins in the membrane act as tiny pumps and push the drug out of the cell before it can cause any harm.

Scientists tried to solve this problem in the following way: they linked numerous doxorubicin molecules with polymer molecules in advance. Polymers embedded in silicon microparticles begin their work when they end up in a tumor.

Specialists injected microparticles into mice that had human liver and lung metastases transplanted. It turned out that silicon particles accumulate near the tumor sites and, once there, they begin to slowly degrade from two to four weeks.

Thus, silicon particles gradually release drug-carrying polymers. In the aqueous medium, next to the tumor cells, polymer filaments, due to thermodynamic forces, curl into tiny balls, each of which is only 20-80 nanometers in diameter. This size, Ferrari believes, is ideal because it is the same as the tiny bubbles that neighboring cells usually exchange.

In this case, the "poisonous" balls are easily absorbed by tumor cells and, accordingly, penetrate into them. They carry the drug through the membrane and are sent towards the cell nucleus. Ferrari says that while scientists do not know exactly why the balls are sent towards the core, although this is exactly what they wanted to achieve.

The area inside the cell around the nucleus has more acidity than near the cell membrane. The team of scientists used this to their advantage. They "designed" the chemical bond between the molecules of doxorubicin and polymer in such a way that it decomposes in an acidic environment. During this process, the drug is released in the place where it is most likely to be able to kill the tumor cells.

This method of treatment has so far been tested only on mice, but it turned out to be very effective. Experiments have shown that up to 50 percent of rodents had no signs of metastatic tumors for eight months after such treatment. According to Ferrari, this may be equivalent to the absence of such signs in a person for 24 years.

The results are so promising that the researchers plan to start clinical trials on cancer patients within a year.

The new study also offers hope for improving the effectiveness of other chemotherapeutic drugs, Libutti says. "There is no reason to believe that it is impossible to make a version of such particles with any other chemotherapeutic substances," he concludes.

The study is described in detail in the scientific journal Nature Biotechnology (Xu et al., An injectable nanoparticle generator enhances delivery of cancer therapeutics).

Portal "Eternal youth" http://vechnayamolodost.ru  16.03.2016