Cellular Service for Drug Delivery

F inding ways to deliver drugs to specific, hard-toreach areas of the human body remains a major challenge in drug development. Drug molecules that enter the body via a pill or an injection circulate in the blood until they reach the target locationa process that can be slow and imprecise. For years, many chemists have been building synthetic nanomotorsnanoparticles that propel themselvesto navigate the vessel-based highways of the body and drop off drugs in specific locations. But these artificial motors typically need fuels like hydrogen peroxide or glucose to run. “The motors that we can build synthetically are vastly inferior to the biological ones”, like bacterial cells or sperm that have built-in mechanisms to help them swim, says Adam Feinberg of Carnegie Mellon University. They’ve been optimized over millions of years and move with minimal energy consumption, he adds. So researchers are now looking to these natural motors to help do the job of drug delivery more effectively. Bacteria, with the help of whip-like structures called flagella, swim efficiently in their environments. Escherichia coli, for example, swim at a consistent rate of 20 to 30 μm per second. Cells like E. coli and sperm can sense and respond to environmental conditions, so they could make a beeline for their target once within range. They could also help minimize exposure of healthy tissues to drugsand therefore reduce side effects by releasing their cargo only after arrival. Recently, several studies have demonstrated a range of viable cargo-carrying swimmers, and researchers are optimistic that these swimming cells could enable a simple yet versatile platform for targeted drug delivery. To prep the cells for drug delivery, they first have to be loaded with a chosen compound. In one example, Metin Sitti of Max Planck Institute for Intelligent Systems and his research group prepared hollow, spherical polystyrene particles with multilayer polyelectrolyte shells about 1 μm in diameter and filled them with the chemotherapy drug doxorubicin. Then they incubated a solution of the nanoparticles with E. coli bacteria for 3 h, allowing them to stick together from electrostatic attraction. On average, each bacterium grabbed one microsphere. The swimmers traveled up to 22.5 μm per second, close to the speed of naked E. coli and faster than previously reported bacterial swimmers of similar size. To bacteria, the human body is vast, so researchers have to help bring them close to their target. Sitti’s team embedded magnetic nanoparticles into the microspheres’ shells so that the swimmers could be guided by an external magnetic field. Another way is to use magnetotactic bacteria that naturally align with and swim along magnetic field lines. Sylvain Martel of Polytechnique Montreal and his group reported using a strain of Magnetococcus marinus bacteria called MC-1 to carry anticancer drugs into tumors within mice. This bacterial species is a good choice for entering tumors, he says, because it likes a low-oxygen environment, which is typically found in tumors. Martel’s team created the swimmers by covering individual MC-1 bacterial cells with over 70 nanosized liposomes containing anticancer drugs. This keeps the overall size of the swimmers under 2 μm, small enough to enter and move around within tumors, says Martel. The researchers tested the swimmers in mice that had colorectal tumors by injecting