Trojan Horse DNA Nanostructures May Be Effective Way to Kill Mesothelioma

Mesothelioma cells have the ability to resist drugs designed to kill them. Here’s how the cancer pulls it off.

First, your doctor infuses your body with a mesothelioma chemotherapy drug such as pemetrexed. The pemetrexed encounters the cells making up a mesothelioma tumor.

The drug then tries to penetrate the individual mesothelioma cells. But the mesothelioma cells instinctively know that letting the drug enter will result in a swift death.

The mesothelioma cells respond by activating tiny efflux pumps that are positioned all along the cell membrane. The pumps force the drug to stay outside the cell.

However, the pumps can be overcome if smacked with a high enough dose of the drug. But a dose of chemotherapy drug can only go so high before it becomes lethal to you.

Because your doctor has to exercise restraint with the administration of chemo, some mesothelioma cells endure the onslaught and survive to grow another day.

Mesothelioma Fooled by Trojan Horse Containing Chemo

Researchers have been tinkering with ways to maximize a chemotherapy drug’s ability to safely overcome this kind of resistance.

One promising approach makes use of a very old and well-known technique for breaching the walls of a military fortress. It’s the Trojan horse strategy.

You remember the story. The ancient Greeks were at war with the city-state of Troy. Troy was an extremely well-fortified target.

For 10 years, the Greeks laid siege to the city but were unable to breach its walls. They decided that the only way to get inside Troy was by trickery. The trick they devised involved building a giant wooden statue of a horse.

The Greeks parked the horse statue in front of the city gates and then withdrew their army. The Trojans opened the city gates, took horse into the city and locked the gates up tight.

The Trojans had a big celebration for what they thought was a huge victory over the Greeks. But when the Trojans fell asleep that night, the Greeks sprung their surprise.

Hidden inside the wooden horse were Greek commandos. They climbed out, unlocked and opened the city gate; in poured the entire Greek army. Troy was quickly conquered.

Today, cancer researchers are using nanotechnology to create microminiature Trojan horses to sneak chemotherapy and other drugs inside tumor cells. In tests, the cancer cells are falling for this trick every time it’s played on them.

Basically, researchers take a manufactured DNA nanostructure loaded with a cancer-killing drug and then offer it to a cancer cell. The cancer cell thinks the DNA nanostructure is food.

The cell doesn’t sense the deadly cargo concealed within the DNA shell. Consequently, the cancer cell greedily gobbles up the nanostructure. The cell then tries to digest the DNA. Doing so dissolves the DNA shell.

This then allows the drug to flood the interior of the cell. The cell tries to spit it out. But it’s then too late. The cell is dead within a matter of hours.

DNA Nanostructures Can Help Fight Mesothelioma

Some of the latest research into Trojan horse DNA nanostructures comes from Ohio State University. Writing in the journal Small, scientists described their success in using the strategy against leukemia cells in the lab.

The Ohio State team hid the antileukemia drug daunorubicin inside DNA nanostructures 15 nanometers wide by 100 nanometers long – about 100 of these could fit inside one cell.

Each Trojan horse consisted of four hollow compartments. The compartments were filled to the brim with daunorubicin molecules.

The researchers used fluorescent markers to keep track of the Trojan horses after they were consumed by the cancer cells. A massive die-off was observed.

The researchers indicate that they are now testing the Trojan horse strategy in mice. If that goes well, they will then test it in humans. But they caution that it could be a few years down the road yet before human testing begins.