Targeted Delivery for Nanoparticles

Conventional chemotherapy can wreak havoc on healthy tissue, causing painful side effects, and it’s not always effective. Nanotechnology-based methods to deliver these drugs only to cancerous cells have shown promise, but they don’t work for all cancers. Now a handful of research groups are developing more-complex approaches that use microscopic carriers to deliver a variety of particles–including drugs, molecular tags that target tumors, and imaging agents to monitor and destroy cancer cells. In theory, these microscopic delivery vehicles would evade the body’s defenses and target blood vessels near a tumor, then release their payload.

While the technology is still in its early stages, researchers at the University of Texas in Houston have taken a first step by engineering tiny discs of porous silicon that can be used to deliver two types of nanoparticles simultaneously. Mauro Ferrari, a professor of biomedical engineering, fabricated porous silicon using previously developed methods and then used photolithography to carve out tiny structures shaped like red blood cells, but about half the size. (Computer models suggest that the structures will tend to hug the inside of blood vessel walls, a crucial property for targeted delivery.)

Ferrari and collaborators then loaded the pores with quantum dots and carbon nanotubes. When administered to cells growing in a dish, the silicon carriers begin to break down, releasing their cargo over the course of several hours. The cells then absorbed the nanoparticles, which accumulated in distinct areas inside the cells. The work was published last month in the journal Nature Nanotechnology.

Ferrari’s approach, and others like it, might overcome some of the drawbacks of current nanotechnology-based drug delivery. In one current technology, hollow, nanoscopic containers called liposomes or micelles are loaded with a drug and injected into the bloodstream. Since the blood vessels that feed tumors tend to be leaky, these nanoparticles tend to accumulate more in tumors than in other tissue. The approach has been approved for use in treating breast cancer and ovarian cancer. But not all tumors have leaky vasculature, Ferrari says, limiting the applications of this approach. His system, on the other hand, can be targeted to cancer cells using antibodies and other targeting molecules, eliminating the need to rely on leaky blood vessels.

Others are already trying a similar approach–using targeting molecules attached to nanoparticles–and, in some cases, are about to begin clinical trials. But unlike liposomes, which can carry significant drug payloads, these nanoparticles only carry a relatively small amount of drug on their surface. What’s more, many of the particles can be trapped or destroyed by the body’s defenses, making it difficult to deliver an effective dose. In Ferrari’s approach, the microscopic silicon carrier would protect the nanoparticles and deliver them in large numbers to the vicinity of the tumor, increasing the chances that the drugs will reach the cancer cells in large amounts.

Multistage approaches such as Ferrari’s are still at an early stage. Robert Langer, a professor of chemical engineering at MIT, calls it a “nice approach,” but points to the need to demonstrate its effectiveness in animals and clinical trials. Other experts disagree whether silicon will be an effective delivery material. James Baker, a physician and professor of biologic nanotechnology at the University of Michigan, says stiff, microscopic particles will likely be trapped in narrow blood vessels. But Michael Sailor, a professor of chemistry and biochemistry at the University of California at San Diego and another leader in the field of multistage delivery, says that silicon particles could be injected close to the tumor, eliminating the need for them to travel through the bloodstream.

If successful, the relatively large microscopic carrier particles could be used as a generic transport for a variety of combinations of drugs and nanoparticles selected for specific types of tumors. This approach could also make it possible to use drugs that have been dismissed for being too easily degraded in the body or too toxic to deliver using conventional approaches. “It is an attack that holds much promise,” says James Tour, a professor of chemistry at Rice University who hopes this approach could be used to deliver some of the tumor-targeting nanoparticles he is developing. “It’s not a sure win, but there is cautious optimism.”