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Drug Delivery

Laser-controlled white blood cells deliver nano-sized cargo

Optical tweezers steer cellular microbots inside a fish’s tail

by Carolyn Wilke, special to C&EN
August 2, 2022


Credit: ACS Cent. Sci.
As a proof of concept for drug delivery, researchers used optical tweezers to spur a white blood cell to pick up a nanoparticle, move it upstream in a blood vessel, and drop its cargo at the target location.

Minuscule robots roving the body and treating disease sounds like something torn from the pages of a sci-fi novel. But researchers have been working to make that scenario a reality. Now, scientists have commandeered white blood cells in zebra fish, turning them into remote-controlled microbots for ferrying nano-sized cargo inside the body and cleaning up cellular debris on demand (ACS Cent. Sci. 2022 DOI: 10.1021/acscentsci.2c00468).

In recent decades, tiny devices that have been tested in living organisms were made of synthetic materials that aren’t fully biocompatible, potentially causing the immune system to attack them like invaders. But in the immune system itself, “the human body already has its own nanomachines,” says Fernando Soto, a nanoengineer at Stanford University who was not involved with the new study. “Let’s just try to communicate with them.”

Chemical biologist Xianchuang Zheng and physicist Baojun Li of Jinan University and their colleagues chose to manipulate neutrophils, the most abundant type of white blood cell in animals. As the immune system’s first line of defense, white blood cells can recognize and clear invading pathogens in the body, Zheng says. The researchers wondered if they could fully control neutrophils—taking advantage of their innate abilities to cross vessel walls and engulf particles—to transform the cells into medical microdevices.

With optical tweezers, which use a highly focused laser beam to control objects, the team maneuvered neutrophils in the transparent tail of a zebra fish. They were even able to use the tweezers to drag white blood cells across a blood vessel wall and into surrounding tissue. Using two laser beams, the researchers could stretch the cells, rousing the neutrophils from rest into an active state like the one they adopt when ready to fight an infection.

Once activated, a neutrophil gobbled up a nearby nanoparticle, and then the team used their optical tweezers to move the cell and drop its payload. Zheng says the cells could help deliver nanoparticle-based drugs that have trouble making it to their target locations. “In our study, we can just drive the neutrophils like a taxi, pick up the nanodrug as the passenger, take them to any position we want, and then drop the nanodrug right on the targeted position.”

Guided neutrophils also cleaned up debris from dead red blood cells. In a similar way, neutrophil microbots could help fight infections by clearing bacteria they are steered to, Zheng says.

“They did a great job of showing proof of concept,” Soto says. And manipulating cells in the body could be a useful tool for learning more about biophysics. But the prospect of using it in medicine is a long way off, he says. Optical tweezers can’t penetrate deeply into tissue. And for animals without transparent skin, the team will also need a way to see into the body so they can see what they’re doing and have a way to adjust.

This is the researchers’ next step. Zheng says they want to control cells in larger animals, perhaps using fiber optics to communicate with neutrophils through the skin.


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