New pneumonia-fighting microbots could be the end of the road for the disease
In a new study, a team of nanoengineers has created a series of micro-robots that can carry medication, swim around in the lungs, and treat life-threatening cases of bacterial pneumonia.
Developed by a team from the University of California San Diego, the microrobots were shown to successfully eradicate the bacteria that causes pneumonia in the lungs of mice, resulting in a 100 percent survival rate!
By contrast, untreated mice all died three days after becoming ill.
You can view the complete study in the journal Nature Materials.
The new tiny robots are made from algae
The tiny robots were built using algae cells with special antibiotic-filled nanoparticles grafted to their surfaces. Because they are so small, the microrobots could "swim" about and administer medications directly to more lung germs because of the algae's mobility.
Each nanoparticle consists of biodegradable polymer spheres with neutrophil cell membranes. For the uninitiated, neutrophils are a type of white blood cell.
These cell membranes are unique in that inflammatory chemicals are produced by bacteria and the body's immune system. The new microrobots can also do this, which enhances their ability to battle lung infection by lowering damaging inflammation.
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 worldwide expert in creating nanoparticles that resemble living cells to treat illnesses and infections.
Together, they have created miniature drug-delivery robots that can safely treat bacterial infections in the blood and stomach of living animals. The most recent aspect of their work involves treating bacterial lung infections.
“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,” he added.
The robots proved to be very effective in mice
The scientists then treated mice infected with Pseudomonas aeruginosa. This bacteria causes severe pneumonia that can prove fatal in some cases.
This type of pneumonia frequently affects patients receiving mechanical ventilation in the intensive care unit.
The researchers delivered the microrobots to their lungs through a catheter placed in the mice's windpipe. After one week, the infections were entirely under control. Mice not given the microrobot treatment died after three days, while every mouse treated with them lived for more than 30 days.
Amazingly, a bloodstream IV infusion of antibiotics was not as effective as the treatment with microrobots.
To accomplish the same impact, the latter needed an antibiotic dose that was 3,000 times larger than what was employed in the microrobots. For instance, an IV injection delivered 1.644 milligrams of antibiotics per mouse, while a dose of microrobots only required 500 nanograms.
The team's strategy works so well because it delivers the medication directly to the patient's area of need rather than dispersing it throughout 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.
The robots could have significant implications for treating pneumonia in humans
Nizet is also a co-author of 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,” he added.
While the new treatment does seem a little intrusive, the researchers are confident that this technique is safe. After treatment, the body’s immune cells efficiently digest the algae and any remaining nanoparticles.
“Nothing toxic is left behind,” said Wang.
The proof-of-concept phase of the project is still ongoing, however. The team plans to conduct further fundamental studies to understand how the microrobots interact with the immune system.
Before testing it on larger animals and eventually on humans, the microrobot treatment will also undergo research to validate and be scaled up.
“We’re pushing the boundary further in the field of targeted drug delivery,” said Zhang.
"Bioinspired microrobots capable of actively moving in biological fluids have attracted considerable attention for biomedical applications because of their unique dynamic features that are otherwise difficult to achieve by their static counterparts. Here we use click chemistry to attach antibiotic-loaded neutrophil membrane-coated polymeric nanoparticles to natural microalgae, thus creating hybrid microrobots for the active delivery of antibiotics in the lungs in vivo. The microrobots show fast speed (>110 µm s−1) in simulated lung fluid and uniform distribution into deep lung tissues, low clearance by alveolar macrophages and superb tissue retention time (>2 days) after intratracheal administration to test animals. In a mouse model of acute Pseudomonas aeruginosa pneumonia, the microrobots effectively reduce bacterial burden and substantially lessen animal mortality, with negligible toxicity. Overall, these findings highlight the attractive functions of algae–nanoparticle hybrid microrobots for the active in vivo delivery of therapeutics to the lungs in intensive care unit settings."
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