An obscure ocean-dwelling bacterium could be just the weapon doctors need to strike directly at the heart of a tumor, according to a new study by a Canadian research team.
The new treatment method uses chemotherapy-carrying bacteria to deliver drugs directly to the low-oxygen regions of tumors, where cancer-promoting activity is thought to be particularly prevalent. Conventional approaches often fail to attack these “hypoxic” areas because they lack the blood vessels that drugs need to reach them and the oxygen required for radiation to be effective. Using chemo-laden bacteria dramatically increased the amount of drug that reached these portions of tumors in mice, although the study did not examine whether this successfully reduced the size of the cancerous masses. The study was published online in August in Nature Nanotechnology.
Modern chemotherapy is like carpet bombing because it is toxic to both cancerous and healthy tissue, said Sylvain Martel, head of the NanoRobotics Laboratory at Polytechnique Montreal and the study’s senior author. “But what we do is we reduce the dose and we put it on a cruise missile and design the GPS system and the sensors to be able to deliver the therapy to a specific location,” Martel said. “We create less collateral damage and a more efficient treatment for the amount of drug that we deliver.”
Martel’s method relies on a species of bacteria called Magnetococcus marinus , which lives in deep-sea waters where oxygen is scarce. The bacteria have the ability to navigate using Earth’s magnetic field, which scientists call magnetotaxis, and they are also able to sense oxygen concentrations. In the wild, these two systems help them find areas of the ocean where they can thrive, but the researchers coopted those abilities to deliver drugs directly to tumors.
First, they attached numerous tiny, chemotherapy-filled sacs called nanocarriers to the bacteria. Then they injected the bacteria into mice and used a magnetic field to guide them to the location of cancer cells that were implanted in the animals. Upon arrival, the microbes’ preference for low oxygen concentrations led them to bury into the masses’ hypoxic zones to deliver their cancer-killing payload.
While nanocarriers have the advantage of shielding healthy cells from their toxic contents, very few of them will reach a tumor without help because they rely on the blood stream to get around. “You inject [them] into the systemic blood circulatory system, which is close to 100,000 kilometers, two-and-a-half times the circumference of the Earth at the equator,” Martel said. “They circulate everywhere, so you need to inject a huge quantity.” And even those that make it to a tumor often cannot access its hypoxic areas. Without guidance, nanocarriers deliver as little as two percent of the chemotherapy dose to tumors, but in Martel’s experiments slightly more than half of the injected bacteria successfully penetrated their targets. This could allow clinicians to use lower doses of chemotherapy.
Prior attempts to target the hypoxic regions of tumors have not had much success because the oxygen concentrations in tumors fluctuate over time, differ in different parts of the tumor, and vary between tumor types, according to Michael P. Hay, an associate professor at the Auckland Cancer Society Research Centre at New Zealand’s University of Auckland. “Hypoxia is definitely of interest but is a hard nut to crack,” Hay said. In addition to overlooking the question of how the treatment affected the tumors, the study also suffers from other limitations. According to Johns Hopkins University oncologist Shibin Zhou, therapies must target parts of tumors with both low and normal oxygen concentrations in order to completely destroy them. Moreover, because the approach was only tested in mice with weakened immune systems, it is unclear if a healthy human body will attack the bacteria, which could set off a life-threatening systemic reaction known as sepsis, said Richard Frankel, an expert in magnetotactic bacteria at California Polytechnic State University.
However, according to Martel, forthcoming research shows that the bodies of mice with normal immune systems do not attack the bacteria, implying the treatment would be similarly safe in humans because the bacteria cannot survive in human hosts. Martel is also confident that it will be more effective than approaches that fail to bring drugs directly to the hypoxic areas of tumors.
“If you have something very efficient and you deliver it to the right location, it’s going to be much more efficient,” Martel said.