TThe lungs are a key target for cancer metastasis. Traditional drug delivery methods rely on passive diffusion. Joseph Wang and Zhang LiangfangThe pair, nanoengineers from the University of California, San Diego, wanted to test an active, targeted system, and in their new study, they explored the possibility of using green algae. Chlamydomonasas A promising platform They are self-propelled, can carry cargo on surfaces, and are biocompatible, making them ideal for drug delivery.1 “This active propulsion plays a key role in improving efficiency,” Zhang said.
Joseph Wang, a bioengineer at the University of California, San Diego, is combining his robotics expertise with his longtime colleague Liangfang Zhang.
University of California, San Diego
Their Survey resultsPublication year Scientific advancesdescribed the development of a biohybrid microrobot from green algae loaded with a chemotherapeutic drug that reduced lung metastasis burden and extended survival in mice.2 Adding additional functionalities to microalgae could further improve drug delivery strategies.
“The green algae act like a mother ship,” Zhang explains, “delivering hundreds to thousands of nanoparticles containing drug molecules.”
The researchers developed the microrobots by chemically attaching nanoparticles (NPs) – biodegradable polymer spheres loaded with the chemotherapy drug doxorubicin (DOX) and coated with red blood cell membrane – to the surface of algal cells. [NP(DOX)]This cell membrane coating protected the drug payload from the immune system.
The team then investigated the properties of the algae-NP(DOX)-robot and used fluorescence and scanning electron microscopes to confirm that the nanoparticles were successfully attached to the microalgae. Comparing the NP(DOX)-robot and the algae-NP(DOX)-robot, the microrobot was more effective at inhibiting the growth and proliferation of cancer cells.
Next, the researchers tested the therapeutic effects of the biorobots over a longer period in mice. “When we administer them to the lungs, the robotic system becomes activated and starts swimming in the lung fluid,” Zhang explained. The researchers administered 70 micrograms of the 75 micrograms of DOX to the lungs of mice and found that more of the algae NP (DOX) robot drug remained in the lungs after 24 hours.
Liang Fang Zhang, a bioengineer at the University of California, San Diego, is blending his leadership in drug delivery and nanomedicine with Wang’s robotics expertise.
University of California, San Diego
The next challenge was to determine how the microrobots were cleared from the body. After 24 hours of incubation with mouse alveolar macrophages, only 25 percent of the DOX from the algae NP(DOX) microrobots was absorbed, compared with 70 percent from the nanoparticles. The researchers suggest that the motility of the microalgae allowed deeper penetration into the lungs and prolonged drug retention.
The researchers then tested the microrobots on mice with lung metastatic melanoma, administering four doses of 75 micrograms of DOX over the course of a week. Bioluminescence showed that the algal NP(DOX) microrobots more effectively inhibited metastasis, extending median survival from 27 to 37 days compared to free drug or NP(DOX) alone.
“Biohybrid [technology] “It’s interesting because it’s a living drug. It can respond to its environment… it definitely has great potential,” he says. Yunus AlapanRobert G. Schneider, a bioengineer at the University of Wisconsin-Madison who was not involved in the work, said he is excited about marrying robotics and biology to create microrobots that can adapt to different microenvironments.
Wang and Zhang plan to test the scalability of these microrobots and explore their therapeutic effects in larger animal models. Additionally, they are exploring other algae, including extremophiles that thrive in harsh environments, to tailor the algae’s diverse properties for specific applications. “The possibilities are endless — think of a multifunctional Swiss knife.” [microrobot] “It’s 20 micrometers… It doesn’t require any batteries or electronics,” Wang said.
