James Baker designs nanoparticles to guide drugs directly into cancer cells, which could lead to far safer treatments.
March/April 2006
Nanomedicine
By Kevin Bullis
This article is the second in a series of 10 stories we're running over two weeks, covering today's most significant (and just plain cool) emerging technologies. It's part of our annual "10 Emerging Technologies" report, which appears in the March/April print issue of Technology Review.
The treatment begins with an injection of an unremarkable-looking clear fluid. Invisible inside, however, are particles precisely engineered to slip past barriers such as blood vessel walls, latch onto cancer cells, and trick the cells into engulfing them as if they were food. These Trojan particles flag the cells with a fluorescent dye and simultaneously destroy them with a drug.
Developed by University of Michigan physician and researcher James Baker, these multipurpose nanoparticles -- which should be ready for patient trials later this year -- are at the leading edge of a nanotechnology-based medical revolution. Such methodically designed nanoparticles have the potential to transfigure the diagnosis and treatment of not only cancer but virtually any disease. Already, researchers are working on inexpensive tests that could distinguish a case of the sniffles from the early symptoms of a bioterror attack, as well as treatments for disorders ranging from rheumatoid arthritis to cystic fibrosis. The molecular finesse of nanotechnology, Baker says, makes it possible to "find things like tumor cells or inflammatory cells and get into them and change them directly."
[To view an illustration of nanoparticles delivering a drug, click here. technologyreview.com ]
Cancer therapies may be the first nanomedicines to take off. Treatments that deliver drugs to the neighborhood of cancer cells in nanoscale capsules have recently become available for breast and ovarian cancers and for Kaposi's sarcoma. The next generation of treatments, not yet approved, improves the drugs by delivering them inside individual cancer cells. This generation also boasts multifunction particles such as Baker's; in experiments reported last June, Baker's particles slowed and even killed human tumors grown in mice far more efficiently than conventional chemotherapy.
"The field is dramatically expanding," says Piotr Grodzinski, program director of the National Cancer Institute's Alliance for Nanotechnology in Cancer. "It's not an evolutionary technology; it's a disruptive technology that can address the problems which former approaches couldn't."
The heart of Baker's approach is a highly branched molecule called a dendrimer. Each dendrimer has more than a hundred molecular "hooks" on its surface. To five or six of these, Baker connects folic-acid molecules. Because folic acid is a vitamin, most cells in the body have proteins on their surfaces that bind to it. But many cancer cells have significantly more of these receptors than normal cells. Baker links an anticancer drug to other branches of the dendrimer; when cancer cells ingest the folic acid, they consume the deadly drugs as well.
The approach is versatile. Baker has laden the dendrimers with molecules that glow under MRI scans, which can reveal the location of a cancer. And he can hook different targeting molecules and drugs to the dendrimers to treat a variety of tumors. He plans to begin human trials later this year, potentially on ovarian or head and neck cancer.
Mauro Ferrari, a professor of internal medicine, engineering, and materials science at Ohio State University, is hopeful about what Baker's work could mean for cancer patients. "What Jim is doing is very important," he says. "It is part of the second wave of approaches to targeted therapeutics, which I think will have tremendous acceleration of progress in the years to come."
To hasten development of nano-based therapies, the NCI alliance has committed $144.3 million to nanotech-related projects, funding seven centers of excellence for cancer nanotechnology and 12 projects to develop diagnostics and treatments, including Baker's.
Baker has already begun work on a modular system in which dendrimers adorned with different drugs, imaging agents, or cancer-targeting molecules could be "zipped together." Ultimately, doctors might be able to create personalized combinations of nanomedicines by simply mixing the contents of vials of dendrimers.
Such a system is at least 10 years away from routine use, but Baker's basic design could be approved for use in patients in as little as five years. That kind of rapid progress is a huge part of what excites doctors and researchers about nanotechnology's medical potential. "It will completely revolutionize large branches of medicine," says Ferrari.
technologyreview.com |
