The idea of using bacteria to fight cancer cells is older than you think. As far back as 1813, French physician Arsène-Hippolyte Vautier made what is considered to be the first written description of bacteria fighting cancer, after noticing that tumours shrank in individuals suffering from gas gangrene, a bacterial infection.
In the two centuries since, while several researchers have tried to harness this capability, none have prevailed. But that might soon change.
Researchers with the help of nanotechnology are working to develop path-breaking methods of using bacteria for the targeted delivery of anti-cancer drugs. They’re also looking at ways to use these bioengineered saviours to stimulate the body’s immune system to destroy cancer cells without damaging our healthy cells.
“Bacterial aided cancer nano-therapies offer great advantages for targeting hypoxic conditions,” says Dr Tanveer Tabish, group leader and principal investigator in nanomedicine at Oxford University in the UK.
The technology could also yield ways to detect cancer earlier, help monitor an individual’s response to drugs, and activate the body’s own immune system to fight cancers. Moreover, these bioengineered bacteria can self-replicate in the host, potentially making the drug cheaper to produce.
Current methods to treat cancers fail on three fronts – it is hard to get the drugs to where they need to be, drugs do not just target and kill cancer cells but also healthy ones, and over time cancer cells are seen to become resistant to drugs reducing the effect of chemotherapy.
The most striking feature of nanoparticle-based bacterial drug delivery platforms according to Dr Tabish is their “capability to facilitate therapeutic interventions while remaining non-toxic to healthy cells and tissue.”
The bacteria can also be used as vehicles to carry antibiotics and natural antimicrobial compounds and release them in a controlled, sustained, and predictable manner. The most common method of using bacterial nanohybrid systems is coupling them with photothermal therapies to kill cancer cells.
But we are just not there yet.
“A further improvement of the system’s active targeting efficiency is necessary,” says Naveneet Dubey, Research Scholar
School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal, Madhya Pradesh. It could take between 8-10 years to complete phase 1 trials before these drugs are brought into testing in the real world.
In the meanwhile, other challenges – loading the drugs onto these nanoparticles, preserving their stability during storage and ensuring that they are manufactured at high-quality – need to be solved. But researchers believe the benefits of these bacterial nanohybrid systems are worth exploring.
No oxygen? No problem
When a tumour reaches a stage when the oxygen supply is not sufficient to feed its growth, it creates what is known as a hypoxic environment where there is a lack of oxygen. This leads to the development of new blood vessels to provide oxygen.
This is the endless loop that leads to metastasis, the spreading of cancer to other parts of the body, and resistance to chemotherapies. Using anaerobic bacteria, those that can survive in an environment without oxygen, in a nanohybrid system can deliver drugs deeper into such tumours.
Trojan horses
When tumours reach this stage and build a self-contained ecosystem, they also become invisible to our body’s own immune system. Sending in bacteria laced with anti-cancer drugs as a trojan horse can also serve to signal the immune cells to reach the tumour site and kill it.
Dubey says that a few groups are working on the challenge of targeting multiple tumour sites with these drugs. “Cancer cells have common characteristics and various tumour sites can be targeted with a single or combination of drugs,” he adds.
Infectious? Or not
Several bacteria cause infections, including some on which these nanohybrid systems are based. But scientists have managed to remove the genes responsible for the bacteria causing infections. In fact, they have been additionally engineered to stimulate an anti-tumour immune response.
Published research shows that this approach is more effective against solid tumours when using noble metals to build the nanoparticles. Dr Tabish says, “silver is one of the most extensively studied nanomaterials that is best suited for binding with bacteria.” Gold is another.
The art of the swim
Another reason for the failure of current cancer therapies is that it’s hard to get the drugs where they need to be. Besides the physical barrier tumours create, getting the drug somewhere is left to our bodily systems. With bacterial systems, this is not the case.
Bacteria can swim. This makes them perfect for reaching into the depths of the tumour tissues and delivering the therapies they carry with them there.
In one experiment, Chinese scientists created a semiartificial bacterium to carry magnetic nanoparticles. After swimming into the hypoxic environment of a tumour, the scientists exposed it to near-infrared lasers to activate the attached magnetic nanoparticles. This destroyed the tumour cells by raising the temperature of the site to as high as 58 degrees Celsius.
Similarly, several others have also created bacteria-based biohybrid nanocarriers as potential cancer therapies. The types of bacteria can vary, as can the nanomaterials and methods to reach the goal of complete tumour destruction without harming the healthy cells of our bodies.
