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Researchers use nanoworms to target tumors in mice
SAN DIEGO—A team of researchers from the University of California, San Diego (UCSD), have developed nanometer-sized "nanoworms" that can cruise through the bloodstream without significant interference from the body's immune defense system and home in on tumors.
The nanoworms could make it easier to image small tumors, allowing cancer to be detected and treated earlier, according to the researchers, whose findings were reported in the journal Advanced Materials.
"We hope it will allow us to locate and identify tumors at a much earlier stage in their growth," says Dr. Michael Sailor, a professor of chemistry and biochemistry at UCSD, who headed the research team, of the finding. "We also hope the materials will allow us to deliver therapies more precisely to specific targets in the body."
The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny, gummy, worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI machines that are used to find tumors.
In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.
The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours, possibly because of the nanoworm's one-dimensional structure.
To date, nanoparticle research has been challenged by the body's natural rejections of foreign bodies, Sailor says.
"The particles have a dextran/peg coating on them that is non-sticky to opsonins, proteins the body uses to remove foreign objects," he says. "The shape seems to evade certain other clearance mechanisms, though it is unclear why at this time."
The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical "ZIP codes," that will allow them to be delivered to specific tumors, organs and other sites in the body, Sailor says.
Other researchers involved in the development were Michael Schwartz of UCSD, Geoffrey von Maltzahn of MIT, and Lianglin Zhang of UC Santa Barbara. The project was funded by grants from the National Cancer Institute of the NIH.