These bacterial microrobots can kill cancer without causing any pain and tears

Preventing the growth of cancer cells in the human body is among the biggest challenges of modern medical science. However, now a team of researchers from the Max Planck Institute for Intelligent Systems claims to have developed an advanced bacteria-mediated therapy to fight cancer-spreading tumors. The proposed treatment involves the use of magnetically guided bacteria-based microrobots as drug carriers. 

The microrobots release drugs directly into the tumors and destroy cancer cells in a painless and effective manner. “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,” said Yunus Alapan, co-author of the study.

During their study, the researchers successfully attached nanoliposomes (spherical vesicles made of lipid that are used for storing drugs inside them) and magnetic nanoparticles to about 86 E. coli bacteria. These special attachments turned the common bacteria into a small army of bacterial biohybrid microrobots.

The science behind bacteria-based biohybrid microrobots

These bacterial microrobots can kill cancer without causing any pain and tears
Nanoliposomes and magnetic nanoparticles attached to E. coli. Source: Birgül Akolpoglu et al. 2022/Science Advances

The numerous nanoliposomes linked to each modified E. coli bacteria are actually vesicles filled with chemotherapeutic drug molecules. Their outer covering can be easily removed by coming in contact with infrared rays. On the other side, the magnetic particles (iron oxide) attached to the bacteria are used to control their movement inside the human body. 

Since E. coli is a highly mobile microbe, the researchers exposed them to a magnetic field. The direction of the magnetic field guided the movement of the iron oxide particles and also the bacteria to which they were attached. Moreover, to link the bacteria with the magnetic particles and nanoliposomes, the researchers used streptavidin-biotin complexes, the most powerful biomolecule binding agents that are often employed to identify new drug targets. 

Streptavidin-biotin complexes are highly stable, and they serve as unbreakable ropes that bind the attachments to the bacteria. While explaining the process further, Birgül Akolpoglu, the lead author of the study said, “Imagine we would inject such bacteria-based microrobots into a cancer patient’s body. With a magnet, we could precisely steer the particles towards the tumor. Once enough microrobots surround the tumor, 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 tumor.”

The researchers claim that the “on-the-spot delivery” of chemotherapeutic drugs using biohybrid microrobots can be accomplished without causing any pain or infection inside the patient’s body. Moreover, with more research and development, it could emerge as one of the most effective treatment strategies against cancer in the future. 

Bacterial microrobots are the perfect match to battle cancer

These bacterial microrobots can kill cancer without causing any pain and tears
Bacteria-based hybrid microrobots moving towards their target under the influence of a magnetic field.  Source: Birgül Akolpoglu et al. 2022/Science Advances

The biohybrid microrobots promise cancer treatment based on an approach called bacteria-mediated therapy (using bacteria to deliver drugs or release enzymes in the human body at desired locations). Surprisingly, this is not a new treatment method, but it has been a tricky one. Many scientists have attempted to equip microorganisms with anti-cancer drugs. 

However, most of them failed because successful treatment using this strategy requires a perfect combination of different techniques. This is where Birgül Akolpoglu and her team managed to get ahead of everyone else. They employed materials that enhanced the capacity of common bacteria and turned the same into highly efficient nanomachines for drug delivery. 

For instance, the nanoliposomes attached to the bacteria consisted of special capsules called the green particles to store the cancer drugs effectively. These particles released the drug only when they came in contact with infrared radiation (a laser beam). Plus, these particles left no scope of interaction between therapeutic molecules and any natural bacterial secretions. 

To overcome movement control-related issues with E. coli, the researchers used the magnetic properties of ferrous oxide particles. Therefore, by integrating robotics and physics with biology, the researchers at Max Planck Institute for Intelligent Systems managed to come up with the perfect components required to overcome the different challenges associated with bacteria-mediated cancer treatment. 

The study is published in the journal Science Advances.

Abstract: 
Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuli-responsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coli with ~90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli–based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.

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