Using lasers to precisely control white blood cells in living fish, researchers have demonstrated that some of the body’s native cells can be “remotely controlled” to accomplish a variety of tasks in a highly precise way. These tasks may someday include biomedical applications such as targeted drug delivery and the precise treatment of inflammatory diseases.

The research team, which included Baojun Li, PhD, and Xianchuang Zheng, PhD, from Jinan University in China, successfully used light-controlled neutrophil “microcrafts” to guide intercellular connections, deliver nanomedicines, and eliminate cell debris in a targeted way. They reported their results in an ACS Central Science article (“Optically Manipulated Neutrophils as Native Microcrafts in Vivo”).

Medical microdevices and microrobots have attracted significant attention in the fields of biotechnology and precision medicine. Those currently in development for medical applications would require injections or the consumption of capsules to get them inside an animal or person. And once inside, the devices can encounter biological barriers (e.g., blood vessel walls). Moreover, most of them are made with synthetic materials that trigger immune responses in vivo.

The researchers’ current work overcomes these obstacles. They used neutrophils—cells already present in the body—to avoid setting off an immune reaction. The neutrophils also have the natural ability to migrate through blood vessels and into adjacent tissues.

“Unlike traditional medical microdevices, this neutrophil microcraft is free from artificial microstructures and invasive implantation processes,” the researchers pointed out. “It exhibits high biocompatibility [and] minor immunogenicity.”

To manipulate the neutrophils, they used highly focused laser beams called optical tweezers. “Optical tweezers have exhibited great potential for manipulating blood cells in vivo,” wrote the researchers, “due to their contactless and noninvasive nature, single-cell precision, and being free from strict limitations on the specific material property.”

Earlier studies had shown that neutrophils could be guided with lasers in lab dishes, moving them around as “neutrobots.” But until now, the feasibility of this approach had not been explored in living animals.

In the current study, the researchers maneuvered neutrophils in the tails of live zebrafish, using focused laser beams as remote optical tweezers. The light-driven microrobots could be moved up to a velocity of 1.3 µm/s, which is three times faster than a neutrophil naturally moves.

They used the optical tweezers to precisely and actively control the functions that neutrophils conduct as part of the immune system. For example, they moved a neutrobot through a blood vessel wall into the surrounding tissue. They manipulated another one to pick up and transport a plastic nanoparticle, showing its potential for carrying medicine. And when the researchers pushed a neutrobot toward red blood cell debris, it engulfed the pieces. Surprisingly, at the same time, a different neutrophil, which wasn’t controlled by a laser, tried to naturally remove the cellular debris.

This work paves the way for the development of microrobots for in vivo biomedical applications, such as the targeted delivery of drugs and the precise treatment of diseases. “This concept [holds] great promise for the active execution of complex medical tasks in vivo, with great potential utility in the treatment of inflammatory diseases,” concluded the researchers.

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