Tiny surgeons battle cancer


Breaking down the microbiology world one bite at a time

Tiny surgeons battle cancer

There is ample “misdirected dread” towards cancer amongst the masses. Although our principal opponent and object of fear must be the tumour, more often than not we find ourselves plagued by the fear of the remedy – the much abhorred but “irreplaceable” chemotherapy. Although chemotherapy is proven to be our most reliable soldier in this war against cancer in the way that it effectively reduces cancer symptoms and can make other procedures like surgery and radiation therapy more effective, there are many flies in the ointment. Chemotherapy has side effects like fatigue, hair loss, anaemia, nausea and some rather serious ones like heart damage and the development of second cancer (delayed effect). 

Efforts, however, are underway to find alternatives to this “necessary evil”. There is a need for a highly specific therapy that targets only the cancerous cells and has minimal side effects on the body and is non-invasive. So how about tiny robots which can be externally directed towards tumours and which deliver the chemotherapeutic drug to the tumour site only. And how about if these robots are our gut bacteria E.coli!! All this has been made possible by scientists in Germany.

Scientists at the Max Planck Institute for Intelligent Systems crossed elements of biology with robotics and have developed magnetically controlled microrobots. The protagonist of this mission was E.coli, which is often deemed the “superhero” of microbial research. It serves as the most ideal choice for the construction of microbots due to its ability to easily sail through varied media ranging from liquid to viscous tissues. The researchers made it possible for three artificial components to be attached to this engineered bacterium.

Image Credit: Akolpoglu et al., Sci. Adv. 8, eabo6163 (2022). doi.org/10.1126/sciadv.abo6163

1) Nanoliposomes: These spherical vesicles are made of lipids and are used to store drugs inside them. These nanoliposomes contain ICG (Indocyanine – a green dye specifically developed for visualisation in the near-infrared region) on their outer surface. ICG particles melt after exposure to near-infrared light. These liposomes enclose chemotherapeutic drug molecules namely doxorubicin (DOX).

2) Iron oxide nanoparticles: This is the magnetic component attached to the bacterium. They help to control the bacteria’s movement inside the body.

3) Streptavidin–Biotin Complex: This complex is very stable and hard to break and acts as a rope to bind the liposomes and the magnetic nanoparticles to the bacterial membrane.

E.coli are highly sensitive, sensory microbes: they are attracted to regions of high acidity and low oxygen levels, both of which are present close to a tumour. To direct these microbes more precisely toward their target (tumour), the scientists can magnetically steer the bacteria in the direction of the tumour, where on exposure to IR rays the nanoliposomes melt and deliver the drug around the tumour.

Simultaneously, the immune system is alerted as a result of the bacteria moving toward the tumour, growing and spreading there, thus eliciting a natural immune response.

Experimental setup demonstrating 3D collagen gels with different stiffnesses with bacterial microbots at one end. Image credits:Akolpoglu et al., Sci. Adv. 8, eabo6163 (2022). doi.org/10.1126/sciadv.abo6163

The researchers at Stuttgart have been successful in combining the three artificial components in 86 out of 100 test microbots. They were able to accurately steer drug-loaded microbots through a setup that resembled microscopic blood vessels towards tumours employing a permanent magnet. Bacteria have been known to have a harder time penetrating through thick matrices like collagen, but the researchers notched up the research by demonstrating that their constructed microbots can penetrate through thick collagen gels.

The researchers have managed to make use of the natural and programmed qualities of E. coli to tackle cancer. Birgül Akolpoglu, the study’s lead author says, “Imagine we would inject such bacteria-based microrobots into a cancer patient’s body. With a magnet, we could precisely steer the particles toward the tumour. Once enough microrobots surround the tumour, we point a laser at the tissue, and that triggers the drug release. Now, not only is the immune system triggered to wake up, but the additional drugs also help destroy the tumour.”

Dr Yunus Alapan, a former postdoctoral researcher in the Physical Intelligence Department, is another researcher in this project. “This on-the-spot delivery would be minimally invasive for the patient, painless, bear minimal toxicity and the drugs would develop their effect where needed and not inside the entire body,” Alapan says.

Written by: Shruchi Singh

Link to the original post: Akolpoglu, M. B, et al. (2022) Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery. Science Advances. doi.org/10.1126/sciadv.abo6163

Featured image: Akolpoglu et al. doi.org/10.1126/sciadv.abo6163