Nanotechnology method to shut down cancer inches toward clinical trials

Having demonstrated a year ago an effective nanotech method for shutting down specific gene expression in a mouse model of colitis, a team of researchers at Tel Aviv University is preparing to test this method in clinical trials for blood, pancreatic, breast and brain cancers. From “A Fantastic Voyage Brought To Life“:

Ever since the 1966 Hollywood movie, doctors have imagined a real-life Fantastic Voyage — a medical vehicle shrunk small enough to “submarine” in and fix faulty cells in the body. Thanks to new research by Tel Aviv University scientists, that reality may be only three years away. The blueprints for the submarine and a map of its proposed maiden voyage were published [last year] in Science [abstract] by Dr. Dan Peer, who now leads the Tel Aviv University team at the Department of Cell Research and Immunology. The team will build and test-run the actual “machine” in human bodies. Dr. Peer originally developed the scenario at Harvard University.…

“Our lab is creating biological nano-machines,” says Dr. Peer. “These machines can target specific cells. In fact, we can target any protein that might be causing disease or disorder in the human body. This new invention treats the source, not the symptoms.” Dr. Peer’s recent paper reported on the device’s ability to target leukocytes (immune cells) in the guts of mice with ulcerative colitis. Calling his new invention a submarine, Dr. Peer has developed a nano-sized carrier which operates like a GPS system to locate and target cells. In the case of Crohn’s disease, for example, it will target overactive immune system cells in the gut. In other diseases such as cancer, the submarine can aim for and deliver material to specific cancer cells, leaving the surrounding healthy cells intact. While other researchers are working in the area of nano-medicine and drug delivery, Dr. Peer’s submarines are among the first to combine a drug candidate with a drug delivery system. As the submarines float through the body, they latch onto the target cell and deliver their payload, a drug based on RNAi. This new kind of drug can affect faulty RNA machinery and reprogram cells to operate in normal ways. In essence, RNAi can essentially restore health to diseased cells or cause cells to die (like in the case of cancer cells).…

Currently, the Tel Aviv University lab is pairing its medical submarine with different RNAi compounds to target different pathologies, such as cancer, inflammation, and neurodegenerative diseases. “We have tapped into the same ancient system the human body uses to protect itself from viruses,” says Dr. Peer, who is also investigating a number of topical applications for his medical subs. “And the beauty of it is the basic material of our nano-carriers is natural,” he says. The Tel Aviv University team plans to launch their medical submarines, following FDA regulations, within three to five years. Their immediate focus is on blood, pancreatic, breast and brain cancers.

In the 2008 Science paper the researchers used a 100-nm nanoparticle made from neutral phospholipids and stabilized by attachment to the outer surface of hyaluronan, a carbohydrate polymer that is one of the major components of the extracellular matrix. To this outer surface they then attached an antibody directed to a molecule called β7 integrin, which is a common surface molecule on the type of white blood cell they wanted to target. Inside they placed an siRNA molecule (bound to protatmine to protect it) that was designed to shut down expression of the molecule cyclin D1, a molecule that regulates cell division. Injecting these nanoparticles into mice suffering from experimentally induced colitis reversed the colitis by suppressing the proliferation of the white blood cells that were causing it. A commentary by Francis Szoka published in the same issue of Science describes the research as a “technical tour de force” and that such studies “highlight the types of targeted systems that may be optimized to provide a robust siRNA delivery to the liver, tumors, and now to the hematopoietic system.” Nevertheless, Szoka cautions that it will be necessary to watch for unwanted immune responses on the part of the patient against some of the components (such as the antibody molecules used for targeting) that go into producing the nanoparticles. (Credit: ScienceDaily for presenting the Tel Aviv University press release.)

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