Stealth Nanoparticles to Target Tumors

Stealth nanoparticles may soon be used to target tumor cells and deliver therapeutic agents to specific body locations, according to scientists.

"Mainly we have focused on chemotherapy drugs,” said Dr. Michael Pishko, professor of chemical engineering and materials science and engineering at Pennsylvania State University (PSU, University Park, USA). "But others are considering using this delivery system to deliver genes in gene therapy.”

The PSU investigators first created nano-sized powders of the medication to be delivered and encapsulated them in a polymer nanoshell. The agent used for this study was palliate, an anti-breast cancer drug, and dexamethasone, a steroid commonly used to treat eye inflammation. This shell allows the drug to move in a stealth-like manner through the bloodstream.

"A layer-by-layer self-assembly technique was used to encapsulate core charged drug nanoparticles in a polymeric nanoshell,” reported the investigators at the 230th American Chemical Society Meeting in Washington (DC, USA) in August 2005.

Typically, drugs--particularly the toxic drugs used for chemotherapy--stimulate the human immune system into action; however, with the polymer shell for protection, these drugs can circulate longer without being removed. "If the drugs do not trigger an immune response, then lower levels of the drug can be used than currently are necessary in chemotherapy,” stated Dr. Pishko.

The researchers assessed their nanoshell method in cell culture and discovered that it had less phagocytes (removal of the drug) during a 24-hour period than the unencapsulated drug. Combined with longer retention in the body, the researchers modified the nanoparticle shells to target certain cells by attaching a functionalized polymer to the shell. They designed this tentacle-like projection to target a receptor on a tumor cell, or a specific location in the eye, for example. Once the agent arrives via the blood to the tumor or eye, it attaches and gradually releases its contents.

This type of drug delivery system works particularly well in such highly vascularized regions such as tumors and the eye, because the drug can travel right up to the target area. Delivery to areas in the brain would not be realistic because of the blood brain barrier that prevents foreign substances from moving from the blood into the cells of the brain.

"For targeting, we could exploit the fact that cancer tumors have a lot more folic acid receptors and target those,” stated Dr. Pishko. "We could also use specific monoclonal antibodies to target specific tumors.” The scientists also are considering delivery of drugs to specific type cells, such as those in the eye. This type of stealth targeting drug delivery system could also be used to deliver genes or gene fragments in gene therapy.