Scurrying tiny creatures with a healing effect: Researchers have transformed flagellated algae into biohybrid microrobots that can actively spread antibiotics in the lungs. On their way through the organ, they slowly release their cargo and can thus damage bacterial pathogens without the entire body having to be treated with antibiotics. The biohybrid robots are then broken down by the organism without leaving any residue. The scientists have already demonstrated the potential of the concept in initial tests on mice: they were able to eliminate pneumonia in a gentle manner.
For some time now, various research groups have been working on futuristic-looking treatment techniques using different methods: One day, microscopic robots could fulfill medical missions in the body – that is the vision. When developing practicable systems, however, scientists are faced with tricky challenges: The microrobots must have drive systems but still have a simple structure so that they can be manufactured in large numbers with little effort. Another aspect is biological compatibility and residue-free degradation: the structures must not cause any immune reactions in the body and must not leave behind any problematic residue after use.
Some developers therefore use biological materials to construct their microrobots. Others, on the other hand, use functional units that are already completely provided by nature as the basis for their systems: They create hybrid robots from the combination of biological "components" or living organisms with technical elements. In the current case, the interdisciplinary research team at the University of California in San Diego used unicellular algae for its development. The interesting aspect of the species Chlamydomonas reinhardtii, in addition to the simple reproduction, is its powerful locomotion system: the green mites have two whipping flagella, with which they can effectively move in their natural aquatic habitat.
Natural propulsion system used
As preliminary investigations by the scientists showed, the algae can also move effectively in liquids such as those found in the bronchial system of the lungs. In order to transform them into biohybrid microrobots for medical use in this organ, the researchers coated the bodies of the protozoa with nanoparticles filled with antibiotics using biochemical processes. These containers are made of polymeric substances that are completely biodegradable. In an appropriate environment, they slowly dissolve, gradually releasing their contents and ultimately leaving no problematic residues. In addition, the nanoparticles were coated with cell membranes of white blood cells to limit possible reactions of the immune system.
To explore the hoped-for impact of the concept, the team used the algal micro-robots to treat mice with an acute form of pneumonia caused by the bacterium Pseudomonas aeruginosa. The researchers emphasize that this test system is clinically relevant: such infections often occur in patients who have to be mechanically ventilated in the intensive care unit. In the experiments, the team introduced the microrobots into the bronchial system of the test animals affected by an acute infection via an inserted tube and examined the effects.
Effectively distributed antibiotics
As they report, the infections caused by this therapy subsided completely after one week: All mice treated with the microrobots survived more than 30 days, while the untreated mice died within three days. There were also no problematic side effects of the treatment, the team reports. It was also shown that the microrobot therapy was significantly more effective than an intravenous injection of antibiotics into the bloodstream. That's because the innovative concept delivers and distributes the drug exactly where it's needed, rather than spreading it throughout the body. As the researchers report, an intravenous treatment required a dose of antibiotics 3,000 times higher than that used in the microrobots to achieve the same effect.
“With an intravenous injection, sometimes only a very small part of the antibiotics reaches the lungs. That's why many current antibiotic treatments for pneumonia don't work as well as needed, leading to high mortality rates in the sickest patients," says co-author Victor Nizet of the University of California, San Diego. "Our previous results in the mouse model show that the microrobots could also optimize the penetration of antibiotics in human patients in order to better kill bacterial pathogens and save lives," says the scientist.
However, as the team concludes, the concept is still in a relatively early stage of development. The researchers will now continue to explore the effectiveness, safety and application potential of their algae microrobots until tests on larger test animals and finally on humans can follow.
Source: University of California at San Diego, professional article: Nature Materials, doi: 10.1038/s41563-022-01360-9