Glowing 'Cornell Dots': Potential cancer diagnostic tool set for human trials

The U.S. Food and Drug Administration (FDA) has approved the first clinical trial in humans of a new technology: Cornell Dots, brightly glowing nanoparticles that can light up cancer cells in PET-optical imaging.

A paper describing this new medical technology is published online in the Journal of Clinical Investigation (July 2011). This is a collaboration between Memorial Sloan-Kettering Cancer Center (MSKCC), Cornell University, and Hybrid Silica Technologies, a Cornell business start-up.

For the first time, scientists report a uniquely advanced and comprehensive characterization of Cornell Dots -- an ultra small, cancer-targeted, multimodal silica nanoparticle -- which has recently been approved as an "investigational new drug" (IND) by the FDA for a first-in-human clinical trial, says Michelle S. Bradbury, M.D., of the Memorial Sloan-Kettering Cancer Center and an assistant professor of radiology at Weill Cornell Medical College.

Cornell Dots are silica spheres less than 8 nanometers in diameter that enclose several dye molecules. (A nanometer is one-billionth of a meter, about the length of three atoms in a row.) The silica shell, essentially glass, is chemically inert and small enough to pass through the body and out in the urine. For clinical applications, the dots are coated with polyethylene glycol (PEG) so the body will not recognize them as foreign substances.

A guiding light within the body: To make the dots stick to tumor cells, organic molecules that bind to tumor surfaces or even specific locations within tumors can be attached to the PEG shell. When exposed to near-infrared light, the dots fluoresce much brighter than dye to serve as a beacon to identify the target cells. The technology, the researchers say, enables visualization during surgical treatment, showing invasive or metastatic spread to lymph nodes and distant organs, and can show the extent of treatment response.

Hooisweng Ow, a coauthor of the paper and once a graduate student working with Ulrich Wiesner, Cornell Professor of Materials Science and Engineering, developed first-generation Cornell dots in 2005. Together, Wiesner, Ow and Kenneth Wang, have co-founded the company Hybrid Silica Technologies (HST) to commercialize the invention. The combined team of MSKCC, Cornell and HST researchers is now in the process of forming a new commercial entity in New York City that will help transition the research into commercial products that will benefit cancer patient care.

"This is the first FDA IND approved inorganic particle platform of its class and properties that can be used for multiple clinical indications, two of which are explored: cancer targeting for diagnostics and future therapeutic diagnostics, as well as cancer disease staging and tumor burden assessment via lymph node mapping," says Bradbury.

The Cornell Dots were optimized for efficient renal clearance, allowing the body to pass them through the kidneys.

In addition, the scientists were able to perform real-time imaging of lymphatic drainage patterns and particle clearance rates, as well as sensitively detect nodal metastases. Nodal mapping is now being pursued under a new award of a BioAccelerate NYC Prize from the Partnership for New York City and the New York City Economic Development Corporation, which is expected to lead to another clinical trial in humans.

The lead authors of the paper are Miriam Benezra and Oula Penate-Medina, who are researchers at MSKCC. Bradbury and Wiesner are the senior authors.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Cornell University, via EurekAlert!, a service of AAAS.

Journal Reference:

Miriam Benezra, Oula Penate-Medina, Pat B. Zanzonico, David Schaer, Hooisweng Ow, Andrew Burns, Elisa DeStanchina, Valerie Longo, Erik Herz, Srikant Iyer, Jedd Wolchok, Steven M. Larson, Ulrich Wiesner, Michelle S. Bradbury. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI45600

‘Cornell dots’ that light up cancer cells go into clinical trials

 "Cornell Dots" -- brightly glowing nanoparticles -- may soon be used to light up cancer cells to aid in diagnosing and treating cancer. The U.S. Food and Drug Administration (FDA) has approved the first clinical trial in humans of the new technology. It is the first time the FDA has approved using an inorganic material in the same fashion as a drug in humans.

"The FDA approval finally puts a federal approval stamp on all the assumptions we have been working under for years. This is really, really nice," said Ulrich Wiesner, the Spencer T. Olin Professor of Materials Science and Engineering, who has devoted eight years of research to developing the nanoparticles. "Cancer is a terrible disease, and my family has a long history of it. I, thus, have a particular personal motivation to work in this area."

The trial with five melanoma patients at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City will seek to verify that the dots, also known as C dots, are safe and effective in humans, and to provide data to guide future applications. "This is the first product of its kind. We want to make sure it does what we expect it to do," said Michelle Bradbury, M.D., radiologist at MSKCC and assistant professor of radiology at Weill Cornell Medical College.

C dots are silica spheres less than 8 nanometers in diameter that enclose several dye molecules. (A nanometer is one-billionth of a meter, about the length of three atoms in a row.) The silica shell, essentially glass, is chemically inert and small enough to pass through the body and out in the urine. For clinical applications, the dots are coated with polyethylene glycol so the body will not recognize them as foreign substances.

To make the dots stick to tumor cells, organic molecules that bind to tumor surfaces or even specific locations within tumors can be attached to the shell. When exposed to near-infrared light, the dots fluoresce much brighter than unencapsulated dye to serve as a beacon to identify the target cells. The technology, the researchers say, can show the extent of a tumor's blood vessels, cell death, treatment response and invasive or metastatic spread to lymph nodes and distant organs. The safety and ability to be cleared from the body by the kidneys has been confirmed by studies in mice at MSKCC, reported in the January 2009 issue of the journal Nano Letters (Vol. 9 No. 1).

For the human trials, the dots will be labeled with radioactive iodine, which makes them visible in PET scans to show how many dots are taken up by tumors and where else in the body they go and for how long.

"We do expect it to go to other organs," Bradbury said. "We get numbers, and from that curve derive how much dose each organ gets. And we need to find out how fast it passes through. Are they cleared from the kidney at the same rate as in mice?"

One of many advantages of C dots, Bradbury noted, is that they remain in the body long enough for surgery to be completed. "Surgeons love optical," she said. "They don't need the radioactivity, but [our study] confirms what the optical signal is. As you learn that, eventually you no longer need the radioactivity."

On the other hand, she added, the dots also may serve as a carrier to deliver radioactivity or drugs to tumors. "This is step one to jump-start a process we think will do multiple things with one platform," she said.

First-generation Cornell dots were developed in 2005 by Hooisweng Ow, then a graduate student working with Wiesner. Wiesner, Ow and Kenneth Wang '77 have co-founded the company Hybrid Silica Technologies to commercialize the invention. The dots, Wiesner said, also have possible applications in displays, optical computing, sensors and such microarrays as DNA chips.

Wiesner's original research was funded by the National Science Foundation, New York state and Phillip Morris USA.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Cornell University.