Researchers at the University of California San Diego have developed a microrobot system to treat bacterial pneumonia. The microrobots consist of living algal cells that can swim very effectively in biological fluids, allowing them to navigate throughout the lungs and deliver drugs to difficult-to-reach areas. The algal cells are studded with antibiotic-loaded polymer spheres that are coated with cell membranes from neutrophils, which help them to neutralize inflammatory molecules that are released by bacteria in the lungs, providing a localized anti-inflammatory effect. In tests in mice with bacterial pneumonia, the microrobots helped to clear the infection. All the treated mice survived for at least 30 days, whereas untreated mice died within three days.
Bacterial pneumonia can have dire consequences for patients, particularly since it can often develop when someone is mechanically ventilated and already in a serious condition. It can also be difficult to treat. Simply administering large doses of antibiotics into the blood stream may not work so well, as very little of the dose ends up where it is needed in the lungs.
There is a need for more targeted and effective therapies. This prompted these UCSD researchers to create a localized therapy that can actively swim into the lungs and deliver drugs exactly where they are needed. “Our goal is to do targeted drug delivery into more challenging parts of the body, like the lungs,” said Liangfang Zhang, one of the creators of the new microrobots. “And we want to do it in a way that is safe, easy, biocompatible and long lasting. That is what we’ve demonstrated in this work.”
Colored SEM image of a pneumonia-fighting microrobot made of an algae cell (green) covered with biodegradable polymer nanoparticles (brown). The nanoparticles contain antibiotics and are coated with neutrophil cell membranes. Images credit: Credit: Wang lab/UC San Diego, Fangyu Zhang and Zhengxing Li
The researchers chose algae as a delivery vehicle for antibiotics. The algal cells are highly adept at swimming through biological fluids, such as the thick mucus that is typically present in the lungs of someone with pneumonia. They attached antibiotic-loaded polymer spheres to the outside of the algal cells, and also coated the spheres in neutrophil membranes for added anti-inflammatory action.
They tested the microrobots in mice with pneumonia caused by Pseudomonas aeruginosa. This type of pneumonia tends to occur in patients who have undergone mechanical ventilation, and it can be life-threatening. The team delivered the microrobots into the lungs using a tube inserted into the trachea. In the treated mice, the infection cleared up after a week, and all survived, whereas the untreated mice died in as little as three days. The approach was also more effective than IV antibiotics, requiring a fraction of the dose to effectively treat the infection.
“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, another researcher involved in the study. “Based on these mouse data, we see that the microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients’ lives.”
