In mice, the microrobots safely eliminated pneumonia-causing bacteria in the lungs and resulted in 100 per cent survival after 30 days compared to the untreated mice that died within three days after infection. The results are published in Nature Materials.
The microrobots are made of algae cells whose surfaces are dotted with antibiotic-filled nanoparticles. The algae provide movement, which allows the microrobots to manoeuvre and deliver antibiotics directly to more bacteria in the lungs. The nanoparticles containing the antibiotics are made of biodegradable polymer spheres that are coated with the cell membranes of neutrophils, which are a type of white blood cell. These cell membranes absorb and neutralise inflammatory molecules produced by bacteria and the body’s immune system, giving the microrobots the ability to reduce harmful inflammation, which in turn makes 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.
“Our goal is to do targeted drug delivery into more challenging parts of the body, like the lungs. And we want to do it in a way that is safe, easy, biocompatible and long lasting,” Zhang said in a statement. “That is what we’ve demonstrated 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, a form of pneumonia that commonly affects patients who receive mechanical ventilation in ICUs.
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The researchers administered the microrobots to the lungs of the mice through a tube inserted in the windpipe, which is more effective than an IV injection of antibiotics into the bloodstream. The latter method requires a dose of antibiotics that was 3000 times higher than that used in the microrobots to achieve the same effect. For comparison, a dose of microrobots provided 500 nanograms of antibiotics per mouse, while an IV injection provided 1.644 milligrams of antibiotics per mouse.
“These results show how targeted drug delivery combined with active movement from the microalgae improves therapeutic efficacy,” said Wang.
“With an IV injection, sometimes only a very small fraction of antibiotics will get into the lungs. That’s why many current antibiotic treatments for pneumonia don’t work as well as needed, leading to very high mortality rates in the sickest patients,” said Victor Nizet, professor at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, who is a co-author on the study and a physician-scientist collaborator of Wang and Zhang. “Based on these mouse data, we see that the microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients’ lives.”
The researchers said that this approach is safe; after treatment, the body’s immune cells digest the algae, along with any remaining nanoparticles.
The work is at the proof-of-concept stage and 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 scaling it up before testing it in larger animals and eventually, in humans.
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