Stealth Particles To Target Tumors

"Mainly we havefocused on chemotherapy drugs," says Michael Pishko, professor ofchemical engineering and materials science and engineering. "But othersare considering using this delivery system to deliver genes in genetherapy."

The researchers first produce nano-sized powders of thedrug they wish to deliver and encapsulate them in a polymer nanoshell.The drug used for this project was paclitaxel – an anti breast cancerdrug – and dexamethasone – a steroid frequently used to treat eyeinflammation. This shell allows the drug to travel in stealth modethrough the bloodstream.

"A layer-by-layer self-assemblytechnique was used to encapsulate core charged drug nanoparticles in apolymeric nanoshell," the researchers told attendees today (Aug. 31) atthe 230th American Chemical Society Meeting, Washington, D.C.

Normally,drugs, especially the toxic drugs used for chemotherapy, trigger thehuman immune system into action, but, with the polymer shell forprotection, these drugs can circulate longer without being removed.

"Ifthe drugs do not trigger an immune response, then lower levels of drugcan be used than currently are necessary in chemotherapy," says Pishko.

Theresearchers, who include Pishko, Alisar Zahr and Cheryl A. Rumbarger,graduate students in chemical engineering, tested their nanoshell incell culture and found that it had less phagocytosis – removal of thedrug – during a 24-hour period than the unencapsulated drug.

Combinedwith longer retention in the body, the researchers engineered thenanoparticle shells to target specific cells by attaching afunctionalized polymer to the shell. They designed this tentacle likeprojection to target a receptor on a tumor cell, or a specific locationin the eye, for example. Once the drug arrives via the blood to thetumor or eye, it attaches and slowly releases its contents.

Thistype of drug delivery system works especially well in such highlyvascularized areas such as tumors and the eye, because the drug cantravel right up to the target area. Delivery to areas in the brainwould not be feasible because of the blood brain barrier that preventsforeign substances from moving from the blood into the cells of thebrain.

"For targeting, we could exploit the fact that cancertumors have a lot more folic acid receptors and target those," saysPishko. "We could also use specific monoclonal antibodies to targetspecific tumors."

The researchers also considered delivery ofdrugs to specific type cells, like those in the eye. This type ofstealth targeting drug delivery system could also deliver genes or genefragments in gene therapy.

The National Science Foundation funded this research.