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Backpacks for Cells

Polymer patches hitched to the surfaces of immune cells can transport a variety of cargo.
November 12, 2008

Living cells wearing microscopic “backpacks”–nanostructured polymer patches loaded with chemical cargo–might one day be able to ferry drugs or imaging agents to diseased tissue. MIT researchers say that they have successfully constructed such backpacks, filled them with magnetic particles, and tethered them to the surfaces of immune cells without disrupting the cells’ ability to interact with their environment. The work is described in a recent issue of Nano Letters.

Geared up: Two immune cells (gray) wear polymer “backpacks” (green). The attached backpacks have two layers: a cell adhesion layer that grabs on to the cell surface, and a payload layer that carries some chemical cargo–in this case, green fluorescent dye. Researchers hope that the backpacks can one day be adapted to deliver drugs or imaging agents to specific regions in the body.

“Overall, this is a very significant piece of work,” says Michael Sailor, a professor of chemistry and biochemistry at the University of California, San Diego, who was not involved in the study. “There are many possible variations on this theme for a host of different diseases. I think it could start an entirely new subdiscipline.”

The backpacks are built from three thin layers of polymer film. The bottom layer anchors the backpack to a surface during construction and loading. The middle layer carries the backpack’s cargo. And the top layer acts as a hook that latches on to a cell’s surface.

Once they had synthesized the backpacks, the researchers added a solution containing living immune cells, which were immediately hooked by the backpacks’ top layers. Then, by lowering the temperature, they triggered the bottom polymer layers to dissolve, releasing the backpack-wearing cells from the surface.

This process allows for incredible versatility in the backpacks’ cargo, says Michael Rubner, director of MIT’s Center for Materials Science and Engineering and senior author of the paper. Because the cells aren’t added until the very end, there’s no danger in using toxic chemicals and harsh conditions to build and load the backpacks. “You can use all the harsh chemistry you want, because the cell isn’t there to be killed,” says Rubner. “It’s only in the last step of the process that the cell attaches to the surface, grabs its backpack, and lifts it off.”

To test how tightly the backpacks attached, the researchers filled them with magnetic nanoparticles, loaded them onto immune cells, and placed the cells near a magnet. Under a microscope, the cells could be seen migrating toward the magnet–tugged along by their backpacks, which stayed firmly anchored in place.

Usually, particles incorporated into a cell’s surface are internalized in a matter of seconds, says Mauro Ferrari, director of the division of nanomedicine at the University of Texas, who was not involved in the work. “The fact that this thing stays there for longer than seconds is remarkable,” he says.

Sailor cautions that while the technology is promising, the real challenge will be getting it to work inside the body. There’s no way of knowing at this stage how the backpack-wearing cells would fare as they circulated in the bloodstream. They might engulf or shed their packs, or lodge in tight spaces. Initial studies suggest that the backpacks don’t pose any danger to the immune cells’ health, but much more work is needed before the system can be tested inside a living animal, says Rubner.

When they do reach the point of animal testing, the researchers plan to start by loading the backpacks with a trackable substance–perhaps the magnetic nanoparticles, which can be imaged by MRI, or perhaps fluorescent molecules. That will allow the team to determine how the cells migrate, and whether they reach the desired targets.

Eventually, Rubner and his colleagues envision using the backpacks for therapies that retool the body’s own immune system to attack diseased or cancerous tissue. For example, immune cells could be removed from the bloodstream, equipped with backpacks, activated to home in on a tumor, and returned to the body. There, they would deliver their cargo–be it an imaging agent or a chemotherapeutic drug–directly to the tumor, sparing healthy tissues from exposure to the toxic payload.

The researchers initially expected that each backpack would adhere uniformly to its carrier cell’s surface, much like a Band-Aid. Instead, the patches seemed to stick firmly at one spot, with the rest dangling off–sort of like a real backpack, which anchors only at the shoulders, says Rubner. This unexpected phenomenon might actually come in handy, he says. Immune cells need to squeeze through narrow openings in the body; a plastered-on pack might make cells less pliable, while a dangling pack could be pulled through.

For the most part, the cells and backpacks hooked up in a one-to-one ratio. But occasionally, under certain conditions, giant clumps of aggregated cells and backpacks formed. Because the backpacks didn’t lie flat against the cells, more than one cell could latch on to a single patch, or more than one patch could attach to a cell. Rubner hopes that his team can learn how to manipulate this process, perhaps serving as a basis for bottom-up tissue engineering.

“This is a new approach,” says Rubner. “There’s a lot of flexibility in what you can do with it, and we’re hopeful that flexibility is going to turn into something that’s going to have great value for society.”

“But that’s going to take a while,” he adds.

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