Robot technology is now used in many fields. Did you know that it is also used in the human body? Over the past 20 years, many microrobots have been developed and used to intervene in anatomically difficult-to-reach areas of the human body.
The microrobots used have yielded successful results in studies conducted on organs such as the stomach, bladder, and lungs. Nevertheless, their performance remains inadequate for applications targeting organs and tissues with complex structures, such as the kidneys, as well as for active drug delivery. In response to this limitation, Zhengxing Li and his team at UC San Diego University developed a biohybrid microrobot using a green algae species called Micromonas pusilla. This organism, which is a picoeukaryote smaller than 3 µm that provided a suitable biological structure for microrobots capable of passing through narrow vascular networks thanks to its size and mobility.
The team designed the microrobot specifically to reach narrow and complex microvascular networks, such as the glomerulus, which forms the filtration unit of the kidney, and to enable active drug delivery. According to the researchers, this approach could improve treatment outcomes in conditions such as chronic kidney disease and end-stage renal disease and provide an alternative to current methods. The team used DBCO-PEG and azido-PEG, special chemicals that allow particles to bind to the microrobot’s surface, to attach magnetic nanoparticles for external guidance and drug-loaded nanoparticles that act as tiny capsules for targeted delivery to the surface of M. pusilla measuring about 1 µm. This biohybrid structure, which can move actively thanks to its flagellum, a whip-like extension that enables movement, was navigated within the body and facilitated targeted drug delivery to the target tissue. The researchers reported observing no adverse health effects due to its biocompatible structure.
In in vivo (live) experiments conducted on mice, the microrobots were capable of remaining in the kidney’s vascular system and intercellular spaces for approximately 48 hours without being captured by the immune system. Researchers compared the 1 µm M. pusilla-based system with the previously developed 10 µm C. reinhardtii-based system in terms of mobility and drug delivery. First, movement tests were conducted in 2D and 3D microchannels. Both systems maintained their mobility in narrow channels; however, the 1 µm system demonstrated a significant advantage over the 10 µm system in narrow spaces. Additionally, at low temperatures and body temperature, the smaller system maintained mobility for longer.
Both microrobots were injected into the renal artery (arteria renalis). Observations indicated that the smaller microrobots easily passed through narrow microstructures such as glomeruli, whereas the larger microrobots could not. The researchers integrated nanoparticles made of PLGA, a biodegradable polymer coated with red blood cell membranes, into both actively moving microrobots and static ‘Static Algae-NP’ microrobots, whose flagella, the whip-like appendages that enable movement, were immobilized using a 250 mM acetic acid solution. These nanoparticles were labeled with DiR (Cy7) fluorescent dye, which served as an experimental tracer, enabling the tracking of the microrobots within the body. This allowed the microrobots’ journey within the body to be tracked. Additionally, the drug delivery and release performance was tested using nanoparticles loaded with ciprofloxacin, a commonly used antibiotic. Both formulations were injected into kidney tissue. After 24 hours, it was determined that the static microrobots remained stationary at their injection site and were quickly eliminated from the body; in contrast, the mobile microrobots advanced within the kidney tissue and actively distributed the drug to the target tissue.
In light of these findings, the M. pusilla-based picoeukaryotic microrobot remained in the tissues for a longer period owing to its small size, flagellar motility, and capacity to evade immune detection. No evidence of significant toxicity was observed due to its biocompatible structure. The findings suggest that these microrobots represent a promising strategy not only for kidney diseases but also for targeting other challenging organs and tissues and treating life-threatening diseases such as cancer.
Author: Burak Can Gürel
Editor: Pelinsu Albey
Reference: Li, Z., Wang, D., Luan, H., Chang, A.-Y., Fang, Z., Sun, L., Ji, J., Shen, W.-T., Yu, Y., Yan, Y., Ding, S., Zhang, J. A., Zhang, Y., Peng, Y., Fang, R. H., Gao, W., Zhang, L., & Wang, J. (2025). Picoeukaryote-based biohybrid microrobots for active delivery in the kidney. Science Advances, 11(28), eadw8578.