Tiny swimming robots treat deadly pneumonia in mice

Microrobots, created by nanoengineers at the University of California, San Diego, can carry medication, swim about in the lungs, and be used to treat life-threatening instances of bacterial pneumonia.

The microrobots successfully eradicated the bacterium that causes pneumonia in the lungs of mice, resulting in 100% survival. In contrast, mice that were not treated all passed away three days after becoming ill.

Nature Materials reported the findings on September 22.

The algae cells used to create the microrobots had antibiotic-filled nanoparticles all over their surfaces. The microrobots may swim about and administer medications directly to more germs in the lungs because to the mobility provided by the algae. The small biodegradable polymer spheres that make up the antibiotic-containing nanoparticles have neutrophil cell membranes coated on them. Neutrophils are a kind of white blood cell. These cell membranes are unique in that inflammatory chemicals generated by bacteria and the body's immune system are absorbed and neutralized by them. The microrobots can do this, which enhances their capacity to battle lung infection by lowering damaging inflammation.

Both Joseph Wang and Liangfang Zhang, professors of nanoengineering at the UC San Diego Jacobs School of Engineering, collaborated on the project. Wang is a global expert in the study of micro- and nanorobotics, and Zhang is a global expert in the creation of nanoparticles that resemble living cells to treat illnesses and infections. Together, they have paved the way for the creation of miniature drug-delivery robots that can be used to safely treat bacterial infections in the blood and stomach in living animals. The most recent aspect of their work is treating bacterial lung infections.

"Our objective is to perform targeted medicine delivery into harder-to-reach areas of the body, such as the lungs. And we want to accomplish it in a way that is long-lasting, straightforward, safe, and biocompatible," added Zhang. "In our work, we have shown that to be the case."

The scientists treated mice with Pseudomonas aeruginosa-caused acute pneumonia using microrobots to prevent death in certain cases. Patients receiving mechanical ventilation in the critical care unit are frequently affected by this kind of pneumonia. Through a catheter placed in the mice's windpipe, the researchers delivered the microrobots to their lungs. After one week, the infections were entirely under control. Mice not given the microrobot treatment perished after three days, but every mouse treated with them lived for more than 30 days.

A bloodstream IV infusion of antibiotics was not as successful as the treatment with the microrobots. In order to accomplish the same impact, the latter needed an antibiotic dosage that was 3000 times larger than what was employed in the microrobots. For instance, an IV injection delivered 1.644 milligrams of antibiotics per mouse, whereas a dosage of microrobots delivered 500 nanograms.

The team's strategy works so well because it delivers the drug directly to the patient's area of need rather than dispersing it throughout the body.

These findings demonstrate how active mobility from the microalgae and focused medication administration might enhance therapeutic effectiveness, according to Wang.

Sometimes, very little of the antibiotics administered by IV will reach the lungs. Because of this, many of the current antibiotic treatments for pneumonia don't work as well as they should, which causes extremely high mortality rates in the sickest patients, according to Victor Nizet, a professor at the UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences and a co-author on the study with Wang and Zhang. The microrobots may be able to increase antibiotic penetration to kill bacterial infections and save the lives of more people, according to the mice study.

And if the idea of inhaling algae cells makes you queasy, the researchers claim that this method is secure. Following therapy, the algae and any lingering nanoparticles are effectively digested by the body's immune cells. Nothing hazardous is left behind, according to Wang.

The proof-of-concept phase of the project is currently ongoing. To precisely understand how the microrobots interact with the immune system, the team intends to do further fundamental study. Prior to testing it on larger animals and eventually on people, the microrobot therapy will also undergo research to verify it and be scaled up.

In the area of tailored medicine delivery, "we're pushing the envelope even farther," added Zhang.

In vivo antibiotic administration via nanoparticle-modified microrobots to treat acute bacterial pneumonia is the topic of the study.

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