Tiny swimming robots treat deadly pneumonia and

image: Color SEM image of a pneumonia-fighting microrobot made from an algal cell (green) coated with biodegradable polymer nanoparticles (brown). The nanoparticles contain antibiotics and are coated with neutrophil cell membranes.
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Credits: Fangyu Zhang and Zhengxing Li

Nanoengineers at the University of California, San Diego have developed microscopic robots, called microrobots, that can swim in the lungs, deliver drugs and be used to clear up life-threatening cases of bacterial pneumonia.

In mice, the microrobots safely removed pneumonia-causing bacteria from the lungs and resulted in 100% survival. In contrast, untreated mice all died three days after infection.

The results are published on September 22 a Materials from nature.

The microrobots are made of algae cells whose surfaces are speckled with antibiotic-filled nanoparticles. The algae provide movement, allowing the microrobots to swim and deliver antibiotics directly to more bacteria in the lungs. The nanoparticles containing the antibiotics are made of small biodegradable polymer spheres that are coated with the cell membranes of neutrophils, which are a type of white blood cell. The special thing about these cell membranes is that they absorb and neutralize inflammatory molecules produced by bacteria and the body’s immune system. This gives the microrobots the ability to reduce harmful inflammation, making them more effective at fighting lung infection.

The work is a joint effort between the labs of nanoengineering professors Joseph Wang and Liangfang Zhang, both at the UC San Diego Jacobs School of Engineering. Wang is a world leader in the field of micro and nanorobotics research, while Zhang is a world leader in the development of cell-mimicking nanoparticles to treat infection and disease. Together, they have pioneered the development of small drug-dispensing robots that can be safely used in live animals to treat bacterial infections in the stomach and blood. The treatment of bacterial lung infections is the latest in his line of work.

“Our goal is to make targeted drug delivery to more difficult parts of the body, such as the lungs. And we want to do it in a safe, easy, biocompatible and long-lasting way,” Zhang said. “That’s what we’ve shown in this work.”

The team used the microrobots to treat mice with an acute and potentially fatal form of pneumonia caused by the bacteria. Pseudomonas aeruginosa. This form of pneumonia commonly affects patients receiving mechanical ventilation in the intensive care unit. The researchers administered the microrobots to the lungs of the mice through a tube inserted into the trachea. The infections disappeared completely after a week. All the mice treated with the microrobots survived after 30 days, while the untreated mice died within three days.

Treatment with the microrobots was also more effective than an IV injection of antibiotics into the bloodstream. The latter required a dose of antibiotics 3000 times higher than that used in the microrobots to achieve the same effect. By comparison, a microbot dose provided 500 nanograms of antibiotics per mouse, while an IV injection provided 1,644 milligrams of antibiotics per mouse.

The team’s approach is so effective because it puts the medication right where it needs to go instead of spreading it throughout the rest of the body.

“These results show how targeted drug delivery combined with the active movement of microalgae improves therapeutic efficacy,” Wang said.

“With an IV injection, sometimes only a very small fraction of the antibiotics will reach the lungs. That’s why many current antibiotic treatments for pneumonia don’t work as well as they should, leading to very high death rates in the sickest patients.” , said Victor Nizet, a professor at the UC San Diego School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. who is a co-author of the study and a medical and scientific collaborator of Wang and Zhang. “Based on this mouse data, we see that microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients’ lives.”

And if the thought of putting algae cells in your lungs makes you cringe, researchers say this approach is safe. After treatment, the body’s immune cells efficiently digest the algae, along with the remaining nanoparticles. “Nothing toxic is left behind,” Wang said.

The work is still in the proof-of-concept phase. The team plans to do more basic research to understand exactly how the microrobots interact with the immune system. Next steps also include studies to validate the microrobot treatment and scale it up before testing it in larger animals and eventually humans.

“We are pushing the limit further in the field of targeted drug delivery,” Zhang said.

Paper title: “Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia.”

This work is supported by the National Institutes of Health (R01CA200574).

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