Tiny device enters cancer cell to deliver killing drug on command

By Ajay Singh

Cancer cells have a new enemy, thanks to a nifty device developed at the Nano Machine Center at the California NanoSystems Institute (CNSI).

Jeffrey Zink, professor of chemistry and biochemistry, and Fuyu Tamanoi, professor of microbiology, immunology and molecular genetics, have led a ground-breaking effort to develop a nanomachine that stores anticancer drugs and, when stimulated by light, releases them inside cancer cells.

Known as a "nanoimpeller" or a "nanobus," the device is the first artificial, light-powered nanomachine that operates inside a living cell. It has highly promising implications for cancer treatment, largely because of its potential role in the precise delivery of drugs.

The nanobus was developed in the chemistry department by Eunshil Choi, a second-year graduate student, under Zink's guidance. The drug-carrying machine is placed inside tiny, spherical nanoparticles of silica that have numerous molecular-sized pores akin to honeycombs.

In an in-vitro laboratory experiment reported in the March 31 online edition of "Small," Zink and Tamanoi brought the nanoparticles in contact with pancreatic cancer cells.

Choi, together with Jie Lu, a postdoctoral fellow in Tamanoi's laboratory, showed that the cancer cells absorbed the nanoparticles through a biochemical process known as endocytosis. When a blue light of a particular wavelength was shone on the nanobuses inside the particles, anticancer drugs were instantly released, killing the cells.

The fact that the mechanism can be operated remotely makes it possible to repeatedly administer small dosages of drugs, thereby increasing their effectiveness and ensuring that only cancer cells — not healthy ones — are targeted. The amount of drugs released is regulated by the intensity and duration of the light.

"External control has been the holy grail of cancer treatment and has not been easy to do," said Tamanoi, who, along with Zink, co-directs the Nano Machine Center for Targeted Delivery and On-Demand Release.

Conventionally, scientists could release anticancer drugs all at once, and the drugs entered cancer cells only gradually (and some drugs didn't reach the tumor at all). In contrast, the nanobus is capable of delivering what Zink and Tamanoi call "on-demand controlled release" of drugs.

"That's the key — a very exciting and important step," said Tamanoi, who also directs the signal transduction and therapeutics program at the Jonsson Comprehensive Cancer Center.

The experiment is the result of a two-year collaboration between researchers in physical science and cancer-cell biology. "Putting our talents together, we can do something wonderful that we couldn't do alone," remarked Zink, adding: "There are still many steps needed before patients can be treated, but we took a big, first step."