“Our goal is to deliver targeted drugs to more difficult parts of the body, such as the lungs. And we want to do that in a way that is safe, easy, biocompatible and long-lasting,” Zhang said. “That’s what we showed in this work.”
The team used the tiny robots to treat mice severely and fatally from pneumonia caused by the bacteria Pseudomonas aeruginosa. This type of pneumonia usually affects patients who receive mechanical ventilation in the intensive care unit. The researchers administered the microbots into the lungs of mice through a tube inserted into the windpipe. The infection was completely gone after one week. All mice treated with microrobots survived the past 30 days, while untreated mice died within three days.
Treatment with microrobots was more effective than intravenous injections of antibiotics into the bloodstream. The latter required a dose of antibiotics 3,000 times higher than that used in microbots to achieve the same effect. For comparison, a dose of microrobots delivered 500 nanograms of antibiotics per mouse, while an IV syringe delivered 1.644 milligrams of antibiotics per mouse.
The team approach is very effective because it puts the drug where it is needed instead of spreading it to the rest of the body.
“These results show how targeted drug delivery combined with the energetic movement of microalgae improves therapeutic efficacy,” Wang said.
“With intravenous administration, sometimes a very small portion of the antibiotics get into the lungs. This is why many current antibiotic treatments for pneumonia do not work as well as they should, which leads to very high mortality rates in the sickest patients,” said Victor Nesette. D., a professor at the University of California, San Diego School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences, is a study co-author and physician and collaborating scientist with Wang and Zhang. “Based on these mice data, we see that microbots can 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 feel allergic, researchers say this approach is safe. After the treatment, the body’s immune cells efficiently digest the algae along with any remaining nanoparticles. “Nothing toxic was left,” Wang said.
Work is still in the proof-of-concept stage. The team plans to conduct more basic research to understand exactly how the microbots interact with the immune system. Next steps also include studies to validate and scale up the microrobot therapy before testing it in larger animals, and eventually in humans.
“We are pushing the boundaries even further in the field of targeted drug delivery,” Zhang said.
Research title: “Nanoparticle-modified microrobots for in vivo antibiotic delivery for the treatment of acute bacterial pneumonia.”
This work is supported by the National Institutes of Health (R01CA200574).