Bio-hybrids against cancer
A group of researchers from the Max Planck Institute for Intelligent Systems modified E.coli bacteria by equipping them with artificial components to create bio-hybrid micro robots. First, the researchers placed several nanoliposomes on each bacterium, which function as a container for therapeutic cargo. Water-soluble molecules of the chemotherapeutic drug doxorubicin (DOX) were placed in the centers of nanoliposomes. The photothermal agent indocyanine green (ICG) was placed around the circumference, which melts under light irradiation with the near infrared spectrum and destroys the liposome membrane, releasing doxorubicin.
The second component that the researchers equipped the bacteria with is iron oxide nanoparticles. When exposed to a magnetic field, they direct bacteria to the target. Liposomes and magnetic nanoparticles are attached to bacteria using a stable and durable complex of streptavidin and biotin, which was developed by the group several years earlier.
Bacterial biohybrid microrobots, after the addition of "cargo", retained their original speed of movement, averaging 18.5 microns/s, and their navigation became possible with the help of an external magnetic field.
E.coli bacteria are fast and versatile swimmers, able to move in a variety of environments, from liquids to highly viscous tissues. In addition, they are attracted to chemical gradients, such as low oxygen levels or high acidity – both are characteristic of the tumor microenvironment.
Cancer treatment by introducing bacteria in close proximity is known as bacterial-mediated tumor therapy: microorganisms accumulate around the tumor, grow there and thus activate the patient's immune system. Bacterial-mediated tumor therapy has been used for more than a hundred years.
Over the past few decades, scientists have been looking for ways to enhance the ability of microorganisms to treat tumors, including placing additional components on bacteria. However, when artificial components are added, complex chemical reactions occur, and the density of particles falling on bacteria is significantly reduced. A group from the Max Planck Institute managed to supply 86% of bacteria with both liposomes and magnetic particles.
The researchers demonstrated the controllability of biohybrids in a liquid medium by guiding them using an external magnet first through an L-shaped narrow channel with tumor spheroids at each end, and then through an even narrower structure resembling small blood vessels. They added an additional permanent magnet on one side and showed how micro-robots loaded with drugs can be precisely controlled in the direction of tumor spheroids. The researchers also conducted micro-robots through a viscous collagen gel, similar in consistency to tumor tissue, with three levels of stiffness and porosity: from soft to medium and hard. The tougher the collagen, the denser the network of protein strands, the harder it is for bacteria to find their way through the matrix. The group showed that with the help of a magnetic field, bacteria manage to go all the way through the fibers.
As soon as the micro-robots accumulate at the desired point (the tumor spheroid), the laser generates near-infrared rays with a temperature of up to 55 degrees Celsius, starting the process of melting liposomes and releasing the drugs contained in them. The acidic environment also leads to the rupture of nanoliposomes – hence, drugs are released near the tumor automatically.
Thus, bio-hybrid micro-robots, accumulating near the tumor, not only activate the immune system, but also release a chemotherapeutic drug. Such minimally invasive and targeted delivery can become a painless, low-toxic and effective strategy for the treatment of oncological diseases.
Article by M.B.Akolpoglu et al. Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery is published in the journal Science Advances.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Max Planck Institute for Intelligent Systems: Bacteria-based biohybrid microrobots on a mission to one day battle cancer.