A team of scientists within the Physical Intelligence Department on the Max Planck Institute for Intelligent Systems have combined robotics with biology by equipping E. coli bacteria with artificial components to construct biohybrid microrobots. Firstly, the team attached several nanoliposomes to every bacterium. On their outer circle, these spherical-shaped carriers enclose a cloth (ICG, green particles) that melts when illuminated by near infrared light. Further towards the center, contained in the aqueous core, the liposomes encapsulate water soluble chemotherapeutic drug molecules (DOX).
The second component the researchers attached to the bacterium is magnetic nanoparticles. When exposed to a magnetic field, the iron oxide particles function an on-top booster to this already highly motile microorganism. In this fashion, it is simpler to regulate the swimming of bacteria – an improved design toward an in vivo application. Meanwhile, the rope binding the liposomes and magnetic particles to the bacterium is a really stable and hard to interrupt streptavidin and biotin complex, which was developed a couple of years prior (https://www.nature.com/articles/s41598-018-28102-9) and is available in useful when constructing biohybrid microrobots.
E. coli bacteria are fast and versatile swimmers that may navigate through material starting from liquids to highly viscous tissues. But that is just not all, in addition they have highly advanced sensing capabilities. Bacteria are drawn to chemical gradients akin to low oxygen levels or high acidity – each prevalent near tumor tissue. Treating cancer by injecting bacteria in proximity is generally known as bacteria mediated tumor therapy. The microorganisms flow to where the tumor is positioned, grow there and in this fashion activate the immune system of patients. Bacteria mediated tumor therapy has been a therapeutic approach for greater than a century.
For the past few many years, scientists have looked for methods to extend the superpowers of this microorganism even further. They equipped bacteria with extra components to assist fight the battle. Nevertheless, adding artificial components is not any easy task. Complex chemical reactions are at play, and the density rate of particles loaded onto the bacteria matters to avoid dilution. The team in Stuttgart has now raised the bar quite high. They managed to equip 86 out of 100 bacteria with each liposomes and magnetic particles.
The scientists showed how they succeeded in externally steering such a high-density solution through different courses. First, through an L-shaped narrow channel with two compartments on each end, with one tumor spheroid in each. Second, an excellent narrower set-up resembling tiny blood vessels. They added an additional everlasting magnet on one side and showed how they precisely control the drug-loaded microrobots towards tumor spheroids. And third – going one step further – the team steered the microrobots through a viscous collagen gel (resembling tumor tissue) with three levels of stiffness and porosity, starting from soft to medium to stiff. The stiffer the collagen, the tighter the net of protein strings, the harder it becomes for the bacteria to search out a way through the matrix. The team showed that when they add a magnetic field, the bacteria manage to navigate all of the approach to the opposite end of the gel because the bacteria had a better force. Due to constant alignment, the bacteria found a way through the fibers.
Once the microrobots are accrued at the specified point (the tumor spheroid), a near infrared laser generates rays with temperatures of as much as 55 degrees Celsius, triggering a melting strategy of the liposome and a release of the enclosed drugs. A low pH level or acidic environment also causes the nanoliposomes to interrupt open – hence the drugs are released near a tumor mechanically.
“Imagine we might inject such bacteria based microrobots right 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 on the tissue and by that trigger the drug release. Now, not only is the immune system triggered to get up, but the extra drugs also help destroy the tumor,” says Birgül Akolpoglu, a Ph.D. student within the Physical Intelligence Department at MPI-IS. She is the primary writer of the publication titled “Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery” co-led by former postdoctoral researcher within the Physical Intelligence Department, Dr. Yunus Alapan. It was published in Science Advances on July 15, 2022.
This on-the-spot delivery could be minimally invasive for the patient, painless, bear minimal toxicity and the drugs would develop their effect where needed and never inside the complete body.”
Dr. Yunus Alapan, former postdoctoral researcher within the Physical Intelligence Department
“Bacteria-based biohybrid microrobots with medical functionalities could sooner or later battle cancer more effectively. It’s a latest therapeutic approach not too far-off from how we treat cancer today,” says Prof. Dr. Metin Sitti, who leads the Physical Intelligence Department and is the last writer of the publication. “The therapeutic effects of medical microrobots in in search of and destroying tumor cells may very well be substantial. Our work is an important example of basic research that goals to profit our society.”
Source:
Max Planck Institute for Intelligent Systems
Journal reference:
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.