Nanoengineers at the
University of California San Diego have developed microscopic robots, called
microrobots, that can swim around in the lungs, deliver medication and be used
to clear up life-threatening cases of bacterial pneumonia.
In mice, the microrobots safely
eliminated pneumonia-causing bacteria in the lungs and resulted in 100%
survival. By contrast, untreated mice all died within three days after
infection.
The results are published Sept. 22 in Nature
Materials.
The microrobots are made of algae cells
whose surfaces are speckled with antibiotic-filled nanoparticles. The algae
provide movement, which allows the microrobots to swim around and deliver
antibiotics directly to more bacteria in the lungs. The nanoparticles
containing the antibiotics are made of tiny biodegradable polymer spheres that
are coated with the cell membranes of neutrophils, which are a type of white
blood cell. What’s special about these cell membranes is that they absorb and
neutralize inflammatory molecules produced by bacteria and the body’s immune
system. This gives the microrobots the ability to reduce harmful inflammation,
which in turn makes them more effective at fighting lung infection.
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. Credit: Fangyu Zhang and Zhengxing Li
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. Wang is a world leader in the field of
micro- and nanorobotics research, while Zhang is a world leader in developing
cell-mimicking nanoparticles for treating infections and diseases. Together,
they have pioneered the development of tiny drug-delivering robots that can be
safely used in live animals to treat bacterial infections in the stomach and blood. Treating bacterial lung infections is the latest in
their line of work.
“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,” said
Zhang. “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.
This form of pneumonia commonly affects patients who receive mechanical
ventilation in the intensive care unit. The researchers administered the
microrobots to the lungs of the mice through a tube inserted in the windpipe.
The infections fully cleared up after one week. All mice treated with the
microrobots survived past 30 days, while untreated mice died within three days.
Treatment with the microrobots was also
more effective than an IV injection of antibiotics into the bloodstream. The latter
required 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.
The team’s approach is so effective
because it puts the medication right where it needs to go rather than diffusing
it through the rest of the body.
“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.”
And if the thought of putting algae
cells in your lungs makes you squeamish, the researchers say that this approach
is safe. After treatment, the body’s immune cells efficiently digest the algae,
along with any remaining nanoparticles. “Nothing toxic is left behind,” said
Wang.
The work is still at the
proof-of-concept stage. 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.
“We’re pushing the boundary further in the field of targeted drug delivery,” said Zhang.
Journal article: https://www.nature.com/articles/s41563-022-01360-9
Spurce: Tiny Swimming Robots Treat Deadly Pneumonia in Mice – Scents of Science (myfusimotors.com)
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