News Release
Breathing in Therapeutic Microrobots Treats Life-threatening Pneumonia in Mice
Inhalable algae-based microrobots can deliver drugs directly to the lungs in an effective prolonged treatment technique, latest research finds.
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| Study authors Zheng Fang (left) and Hao Luan (right) use a nebulizer to deliver algae-based microrobots inside a treatment chamber. Photo by David Baillot / UC San Diego Jacobs School of Engineering |
May 6, 2025
Engineers at the University of California San Diego found a new non-invasive way to deliver pneumonia-treating microrobots to the lungs: by making them breathable. The team determined that aerosolizing their algae-based microrobots with a nebulizer achieved the desired long-lasting and uniform distribution of the drug-delivering microrobots in the lungs.
For mice with life-threatening cases of acute pneumonia, inhaling these drug-carrying microrobots significantly reduced the bacterial load in their lungs and resulted in a 100% survival rate over a 60-day study period. The mice in the control groups, in contrast, died within three days. These results are detailed in a paper published Jan. 14 in Nature Communications. (Read a non-techical desciption of this project which is written specifically for the general public.)
The work marks another promising step in a long-standing collaborative effort between the labs of Joseph Wang and Liangfang Zhang, both professors in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at the UC San Diego Jacobs School of Engineering. While they have teamed up before to develop tiny drug deliverers to treat other parts of the body, they have been tackling the lungs most recently.
“The lung is a challenging organ for drug carriers to access and achieve even distribution throughout the tissue and long retention within the tissue,” said Zhang.
The patient-friendly method the team landed on involved a nebulizer system that encapsulates the microrobots within small liquid aerosol particles, which can then be inhaled through normal breathing.
Drug-delivering microbots
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| Colored scanning electron microscope (SEM) image of an algae microrobot (green) carrying vancomycin-loaded nanoparticles (brown). The scale bar is 500 nanometers. Credit: Professor Joseph Wang and Professor Liangfang Zhang Labs |
The research team previously developed microrobots to treat a deadly bacterial-caused pneumonia and metastatic cancer tumors directly in the lungs. These microscopic robots are made of live algae cells, dotted with nanoparticles containing disease-tailored drugs. The active algae provides the microrobot with propulsion, allowing it to swim around inside the lung tissue and distribute the medication throughout.
“Our early studies demonstrated the role of the long-lasting algae motion upon the improved treatment of these diseases via substantially enhanced retention and distribution of the algae and its payload throughout the lung,” said Wang.
The microrobots in those studies however were administered through a tube inserted into the windpipe, which requires anesthesia. Given the invasiveness of that type of procedure, the team decided to explore methods to deliver microrobots to the lungs with little to no discomfort for the patients.
For aerosols, size matters
In order for microrobot-carrying aerosols to reach the lungs without being trapped in the upper respiratory tract, they need to be a certain size: smaller than 10 micrometers, explained first-author Zhengxing Li. Li was a nanoengineering Ph.D. student in both Wang and Zhang’s research groups at the time of the study and now is a joint postdoctoral researcher.
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| Illustration of how a nebulizer (a) aerosolizes (b) the microrobots to administer them to the lungs of a mouse (c) through normal breathing. Credit: Professor Joseph Wang and Professor Liangfang Zhang Labs and David Baillot / UC San Diego Jacobs School of Engineering |
Given that ideal size range, the specific algae used to make the microrobots in the prior studies are actually too large. So the researchers turned to another type of green algae, Micromonas pusilla, which is much smaller (about 1–1.5 micrometers).
An additional benefit to this smaller algae is its speed. The research team has been designing their microrobots around algae partly because they can escape the immunoprotective system of the lungs, namely the fast macrophage—a type of white blood cell that detects and consumes foreign debris to remove it from the body. By optimizing the concentration of the microrobots and nebulizer flow rate, the team was able to ensure that the microrobots maintained a speed of about 55 micrometers per second once inside the lungs. The researchers are able to detect and track the microrobots, thanks to the autofluorescence of the chlorophylls in the algae.
With that speed, the microrobots can swim around to deliver their nano-sized packets of medication (the antibiotic vancomycin in this study) throughout the lungs. According to Li, if those nanoparticles were administered directly to the lungs without the self-propelling microrobots, they would be quickly destroyed by the macrophage given their staticity and minuscule size.
Lower dosage
As a safety measure, the customizable medicine packets carried by the algae are actually covered in a platelet-membrane, which helps disguise the particles from being detected as foreign objects by the immune system. With that protection and that the microrobots are able to stay active in the lungs for more than five days, the overall treatment has a long retention time.
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| The nebulizer sprays aerosolized microrobots into the treatment chamber. Photo by David Baillot / UC San Diego Jacobs School of Engineering |
“When you can increase the retention time, you can reduce the drug dosage,” said Li. “It’s a better way to achieve the same treatment efficacy.”
That’s because higher doses of drugs can cause more problems from drug side effects. Traditional treatment methods, like intravenous injections, typically use drug dosages about 300 times larger than what was needed with this new method, said Li.
“A major limitation of current lung drug delivery systems is their reliance on passive diffusion, which restricts both the distribution and retention of the formulations in lung tissues,” said Zhang.
For this study with mice, the research team used a treatment chamber with the nebulizer system. That allowed the mice to breathe and behave normally while inside the chamber during the administration. For humans though, the researchers envision that the aerosols can be delivered via a mouthpiece or mask, and they plan on scaling the approach toward that use.
And they don’t feel limited to just treating pneumonia, as Wang said, “Next, we will exploit the major benefits of nebulizer-based inhalation delivery of these drug-functionalized algae toward various important lung diseases.”
Paper: “Inhalable biohybrid microrobots: a non-invasive approach for lung treatment.” Co-authors of the study include Zhengxing Li*, Zhongyuan Guo*, Fangyu Zhang*, Lei Sun*, Hao Luan, Zheng Fang, Jeramy L. Dedrick, Yichen Zhang, Christine Tang, Audrey Zhu, Yitan Yu, Shichao Ding, Dan Wang, An-Yi Chang, Lu Yin, Lynn M. Russell, Weiwei Gao, Ronnie H. Fang, Liangfang Zhang and Joseph Wang.
*These authors contributed equally to this work.
This work was supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense (HDTRA1-24-1-0019 and HDTRA1-21-1-0010).
Media Contacts
Liezel Labios
Jacobs School of Engineering
858-246-1124
llabios@ucsd.edu