Small floating robots treat deadly pneumonia and

photo: SEM color image of a microrobot fighting pneumonia, made of an algae cell (green) coated with biodegradable polymer nanoparticles (brown). The nanoparticles contain antibiotics and are covered with neutrophil cell membranes.
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Source: 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 treat life-threatening cases of bacterial pneumonia.

In mice, the microrobots safely eliminated the pneumonia-causing bacteria in the lungs and provided 100% survival. In contrast, all untreated mice died within three days of infection.

The results were published on September 22 in Natural materials.

Microrobots are made of algae cells, the surfaces of which are dotted with nanoparticles filled with antibiotics. The algae provide movement that allows the microrobots to swim and deliver antibiotics directly to more bacteria in the lungs. The antibiotic-containing nanoparticles are made up of tiny biodegradable polymer spheres that are covered with neutrophil cell membranes, which are a type of white blood cell. The special feature of these cell membranes is that they absorb and neutralize inflammatory molecules produced by bacteria and the body’s immune system. This allows microrobots to reduce harmful inflammation, which in turn makes them more effective at fighting lung infections.

The work is a collaborative effort by the laboratories of nanoengineering professors Joseph Wang and Liangfang Zhang at the University of California, San Diego Jacobs. Wang is a world leader in micro- and nanorobotics research, while Zhang is a world leader in the development of cell-mimicking nanoparticles for the treatment of infection and disease. Together, they are pioneering the development of tiny drug delivery robots that can be safely used in live animals to treat bacterial infections in the stomach and blood. Treatment of bacterial lung infections is new to their work.

“Our goal is the targeted delivery of drugs to more demanding parts of the body, such as the lungs. And we want to do it in a safe, easy, biocompatible and long-lasting way, ”said Zhang. “This is what we showed in this work.”

The team used microrobots to treat mice with the acute and potentially fatal form of bacterial pneumonia Pseudomonas aeruginosa. This form of pneumonia often affects patients undergoing mechanical ventilation in the intensive care unit. Scientists introduced microrobots into the lungs of mice through a tube placed in the trachea. The infections completely resolved after a week. All microrobot-treated mice survived for more than 30 days, while untreated mice died within three days.

Treatment with microrobots was also more effective than the intravenous injection of antibiotics into the bloodstream. The latter required a dose of antibiotics 3,000 times greater than that used in microrobots to achieve the same effect. For comparison, a dose of microrobots delivered 500 nanograms of antibiotics per mouse, while intravenous injection delivered 1.644 milligrams of antibiotics per mouse.

The team’s approach is so effective because it puts the drug exactly where it should, rather than distributing it through the rest of the body.

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

“With an intravenous injection, sometimes only a small fraction of the antibiotics will enter the lungs. That is why many of the current antibiotics to treat pneumonia do not work as well as necessary, leading to very high mortality among the sickest patients, “said Victor Nizet, professor at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. . who is the co-author of the study and associate of the physician-scientist Wang and Zhang. “Based on this data from mice, we can see that microrobots have the potential to improve the penetration of antibiotics by killing bacterial pathogens and saving more patients’ lives.”

And if the thought of putting algae cells in your lungs gives you the chills, scientists say it’s safe to do so. After the treatment, the body’s immune cells efficiently digest the algae along with other nanoparticles. “Nothing toxic is left,” said Wang.

The work is still at the concept verification stage. The team plans to conduct more basic research to understand in detail how the microrobots interact with the immune system. The next steps also include studies to validate and scale up microrobot treatment before testing in larger animals and ultimately in humans.

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

Title of the article: “Microrobots modified with nanoparticles for the in vivo administration of antibiotics in the treatment of acute bacterial pneumonia”.

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

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