Lung cancer, CT
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Scientists have engineered algae-based microrobots capable of swimming through the lungs to deliver chemotherapy directly to the lungs. In mouse models of melanoma, the treated mice reduced tumor growth and spread and improved survival.

The findings are detailed in a paper published on June 12 in Science Advances.

The microrobots were developed several years ago in the labs of Joseph Wang and Liangfang Zhang at the UC San Diego Jacobs School of Engineering. In 2022, they published a paper in Nature Materials showing that the approach using a different drug and cell membrane combination for the nanoparticles was effective in treating pneumonia in mice.

In the current study, mice with melanoma that had metastasized to the lungs were treated with doxorubicin-loaded microrobots administered to the lungs through a small tube inserted into the trachea. Treated mice survived a median survival of 40 days compared with the 27-day median survival time observed in untreated mice and mice that received either the drug alone or drug-filled nanoparticles without algae. Some of the mice survived up to 55 days.

The microrobot algae platform consists of natural green algae cells attached to red blood cell membrane-coated doxorubicin (DOX)-loaded polymeric poly(lactic-co-glycolic acid) (PLGA) nanoparticles. “The drug-loaded nanoparticles are loaded onto the algae surface which carries them deep into the lungs where it is difficult to remove the algae and the drug,” says study co-first author Zhengxing Li, who is a nanoengineering PhD student in both Wang and Zhang’s research groups.

The algae, which provide the microrobots with their movement, enable the nanoparticles to efficiently swim around in the lungs and deliver their therapeutic payload to tumors. The red blood cell membranes protect the nanoparticles from the immune system, allowing them to persist in the lungs to kill cancer cells.

“It acts as camouflage,” Li adds. “This coating makes the nanoparticle look like a red blood cell from the body, so it will not trigger an immune response.”

The prolonged swimming of microalgae facilitates the efficient distribution of chemotherapeutics throughout the lungs, providing an effective strategy for treating lung metastasis. Li explains an additional benefit: The active motion of the algae makes it difficult for macrophages to capture the algae microrobot and destroy it before it is well distributed throughout the lungs.

The biodegradable PLGA nanoparticles encapsulate the anticancer drugs for controlled release, while the cell membrane coating imparts biomimetic properties that shield the therapeutic payload from the biological environment. In their experiments, the microrobots retained their intrinsic motion capabilities even under physiological conditions.

Through intratracheal administration of the microrobots into the lungs of mice, the team demonstrated enhanced distribution and prolonged presence, resulting in a more effective accumulation of the loaded drugs. They conclude that this results aligns with the slow uptake of biohybrid robots by alveolar macrophages, which is likely a consequence of the unique motion capabilities of the microalgae carriers.

“Overall, there is a substantial improvement in therapeutic efficacy against melanoma lung metastasis, as evidenced by the reduced lung metastatic burden and substantially improved median survival time compared to passive drug-loaded nanoparticles and free drug controls,” the authors write.

The team explains that the platform is not limited to just one drug. “The nanoparticles can be hydrophobic or hydrophilic depending, and can be loaded with different types of drugs depending on the job,” says Li.

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