By loading genes onto nanoparticles, then attaching the nanoparticles to bacteria, scientists have devised a new way of shuttling potentially therapeutic material into mammalian cells. Because the nanoparticles could carry a variety of molecular cargo, the system could have a wide range of applications, including cancer therapy and insertion of cellular biosensors.
Rashid Bashir and his colleagues at Purdue University in West Lafayette, Ind., worked with Listeria monocytogenes, which are bacteria with molecular machinery that can penetrate a cell’s defenses. The recipient cells naturally package the cargo-coated bacteria, which the researchers call “microbots,” in a fatty envelope and bring them inside. Bacterial proteins then poke holes in the cellular packaging and release the nanoparticles and their cargoes.
To demonstrate the technique, the researchers attached fluorescent genes to polystyrene nanoparticles and loaded Listeria cells with the two-part cargo. They applied the microbots to human cells cultured in the lab or put them into living mice. Successful delivery produced glowing cells. Up to 40 percent of the cells incorporated the genetic cargo, Bashir and his colleagues report in the July Nature Nanotechnology.
An established technique using genetically modified bacteria to deliver a desired gene achieves only 2 to 20 percent efficiency, the researchers say. Moreover, the microbots can haul more than one type of gene or molecule at a time. Changing the cargo is as simple as swapping the nanoparticles, says Purdue’s Demir Akin. “The cargo can be anything.”
Other researchers have tried a variety of strategies to deliver molecules into cells. For example, they have slipped molecules inside fatty envelopes called liposomes. But liposomes move passively through the body. And although they can efficiently bring cargo into cells, that cargo can then be hard to unpack, Bashir says. An alternative is to use viruses, which, like bacteria, can deliver a gene to a target cell, says Guido Dietrich of Berna Biotech AG, a vaccine manufacturer in Berne, Switzerland. However, involving viruses in such a procedure risks an infection that can’t be controlled with drugs.
The new technique could also be limited by the risk of infection, but bacteria can be killed by antibiotics, Bashir and Akin point out. In fact, Listeria bacteria aren’t approved for use in humans and are toxic to mice, so the researchers dosed the animals in their experiments with antibiotics. They are already planning to use bacterial strains that don’t cause disease. “Live bacteria have been in use for decades as an active ingredient of . . . vaccines against tuberculosis and typhoid fever,” Dietrich says. If such strains can be used, “there should be no safety issue,” he says.
Because the bacterial microbots can deliver their loads efficiently and to specific cells, the technique could be particularly suitable for targeted cancer therapy, the researchers say. Such a system would deliver drugs in safe doses or in tailored combinations directly to the cells that need treatment.
