Red Blood Cells Release Cargo On Demand

Red blood cells could be an ideal vehicle for drug delivery: They’re naturally compatible with the immune system and circulate for days in the body. So far, researchers have found easy ways to load the cells with drugs, but the challenge has been to release these molecules at the right place. Now a German team shows that by decorating cargo-filled red blood cells with gold nanoparticles, they can trigger them to dump their contents with a zap from a laser (ACS Nano, DOI: 10.1021/nn3006619).

At least two European pharmaceutical companies have started clinical trials to test drug-carrying red blood cells as a way to treat leukemia and other immune and inflammatory diseases. To load these cells, researchers place them in solutions with a lower salt concentration than what’s found in the body. Due to the difference in osmolarity between inside and outside the cell, small pores open up in the cell membranes, and drugs in the solution rush into the cells. The drugs then spill out in the body when white blood cells consume the red cells, a normal physiological process, says Hans Bäumler of Charité-Universitätsmedizin Berlin.

But this release mechanism only works for diseases involving white blood cells. To deliver cancer drugs to a solid tumor, the cells would need to precisely time the release of their payload near it. Bäumler and his colleagues wanted to devise a method to trigger release that was noninvasive and left the red blood cells intact.

So they coated cargo-filled red blood cells with gold nanoparticles, which heat up when hit with an infrared laser. The team believes that the heat changes the structure of lipid or protein molecules in the cells’ membranes, creating short-lived pores for the cargo to escape through.

To see if the method would work, the researchers filled red blood cells with two cargo molecules of different sizes: a small green dye and a larger, red dye-labeled biopolymer. They then mixed a suspension of the cells with gold nanoparticles and allowed the particles to adsorb on the cells’ surfaces.

While observing the cells using fluorescence microscopy, the scientists applied a pulse from an infrared laser on individual cells. Within seconds, each cell stopped glowing, a sign that the dye molecules had left the cell. The researchers say that they can control the size of the membrane pores by tuning the power of the laser pulse. A high power pulse produces a large pore. They think that by changing the laser power they could selectively release cargo molecules based on size.

Mario Magnani, of the University of Urbino, in Italy, calls the method novel and interesting, especially because it appears to leave the red blood cells intact. However, he sees two practical problems: Infrared light doesn’t penetrate deeply into body tissue, making many tumors difficult to access with the technique’s laser. And the immune system’s white blood cells would quickly attack the red blood cells because they would recognize the gold-nanoparticle coating as foreign.

Andre Skirtach of the Max Planck Institute of Colloids and Interfaces, a coauthor on the new study, admits that the technology will work best “for areas close to the skin surface.” But he says that one solution for deep tumors could be to send laser light through a hair-thin optical fiber.

He hopes to make the technology more effective by directing red blood cells to tumors. The team could do this either by decorating the surface of the cells with antibodies that bind only to tumor cells, or by loading them with magnetic particles and then steering them to a tumor with a magnet.