For most cancer patients, it is not the original tumor that poses the greatest risk. It is the metastases that invade the lung, liver and other tissues. Now, researchers have developed an approach that tricks these tumors derived by swallowing poison. So far, the strategy has been tested in mice, where it has proven very effective. But the results are promising enough that the researchers plan to launch clinical trials in cancer patients within a year.
The new work is "very innovative stuff," says Steven Libutti, a geneticist and cancer surgeon at the Albert Einstein College of Medicine in New York, who was not involved in the study. The treatment, he explains, works in three steps to place a conventional chemotherapeutic agent near the core (or cores) of a metastatic cancer cell where the drug molecules are the deadliest. "It's almost like a multistage rocket" which lifts the astronauts out of Earth, sends them to the moon and return safely, he said.
At the heart of the new therapy is a chemotherapy drug called doxorubicin (Dox). the drug has been a mainstay of cancer treatment for years, because it blocks the DNA in the cell nucleus and prevents tumor cells from dividing. But when it is injected into the circulation blood, the drug can also kill cells of the heart muscle and cause heart failure, which often requires oncologists or reconstruct the dose or stop completely. Delivering dox only to tumor cells is highly desirable, but it was a challenge major.
hoping to provide such cell specificity, researchers led by Mauro Ferrari, an expert in nanomedicine, and president and CEO of the Houston Methodist Research Institute in Texas, spent years developing porous silicon particles as drug carriers. the micrometric scale particles and disc-like shape allows them to travel freely throughout the normal blood vessels. But when they hit the blood vessels around tumors, which are typically malformed and leaking, the particles fall out of traffic and the pool near the tumor. This was the first step in delivering chemotherapy drugs to their target. But just fill these particles with dox does not do much good, says Ferrari. Even if a small amount of the drug finds its way inside tumor cells, cells often have membrane proteins that act as tiny pumps to push the drug back out of the cell before they can do damage.
silicon particles act as nanoparticles generators (INPG) that carry charged polymers type string of a chemotherapeutic compound known as doxorubicin (p-Dox).
Nature Biotechnology
To obtain large amounts of dox within the metastatic tumor cells, and then past the protein pumps, Ferrari and colleagues linked many molecules of Dox molecules called polymers rope. They then perfused polymers bearing Dox in their micro-particles of silicon and injected into mice who had been implanted with tumors of the liver and metastatic human lung. As in previous studies, the researchers found that the silicon particles gathered in and around the tumor sites, and once there, the particles slowly degraded over 2 to 4 weeks.
As they did, the silicon particles released dox -carrying polymer strands. In the aquatic environment surrounding the tumor cells, wound strands in tiny balls, each only 20-80 nanometers. This size, Ferrari said, is ideal, since it is the same size as the tiny vesicles which are routinely exchanged between neighboring cells as part of their normal chemical communication. In this case, the dox-polymer beads were readily taken up by tumor cells. Once there, much was done in Internal away pumps dox exporters cell membrane to the nucleus. Ferrari said at the time that his team does not know exactly why dox loaded balls are transported to the nucleus, although that is exactly what they wanted.
Not only is the region around the core devoid of dox- removing pumps, but it typically has a more acidic environment near the cell membrane. And the Ferrari team used to their advantage as well. They designed chemical bonds between the molecules of Dox and the polymer to dissolve in acidic conditions. This frees the dox where its destructive power of the cells is higher.
Up to 50% of cancer-bearing mice given the treatment showed no evidence of metastatic tumor eight months later, the researchers report today in Nature Biotechnology . In humans, Ferrari said, this is equivalent to being cancer free for 24 years. "If this research involves humans and we see even a fraction of that time to survive, we talk yet greatly extend life for many years," said Ferrari. "This essentially provides a cure in a population of patients now says there is not. "
the new treatment is not the first nanomedicine to show promise. According to a recent study of nanotechnology working group published in the Lancet , more than 50 Nanomedicine compounds are now in clinical trials. However, the new work is promising, Libutti said, because the silicon microparticles tend to target liver tumors and lung tumor cells of common destinations metastatic.
the new work holds the hope of improving the effectiveness of other chemotherapy drugs as well, Libutti said. "There is no reason to believe that you could not make a version of these particles with a chemotherapeutic agent. "
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