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One of the hallmarks of many nanoparticle-based anticancer therapeutics and imaging agents is that they accumulate in tumors thanks to the fact that they are small enough to escape from the bloodstream through the leaky blood vessels that surround tumors. And although many if not most tumors are surrounded by leaky blood vessels, the extent of that leakiness varies widely among tumors. As a result, the effectiveness of a given nanoparticle-based therapeutic also might vary from patient to patient in a way that is now impossible to predict.
A research team headed by Ravi Bellamkonda, Ph.D., the Georgia Institute of Technology, appears to have hit on a solution to the problem of determining how much of a nanoparticle drug is actually making it into breast tumors. The team's approach, which is described in a paper in the journal Biomaterials, involves adding an approved x-ray contrast agent to a drug-loaded nanoparticle and then using standard mammography to quantify how much of the nanoparticle accumulates in a particular breast tumor. These results hold promise for personalizing breast cancer therapy.
To create their nanoparticle, the investigators first prepared a highly concentrated solution of the x-ray contrast agent iodixanol and then added two different lipids, one of which was linked to PEG. The resulting lipd-based nanoparticles then were mixed with the anticancer agent doxorubicin for 1 day, yielding a nanoparticle loaded with both anticancer agent and contrast agent.
The investigators then administered this nanoparticle to rats with human breast tumors using a dose that was small enough so that only nanoparticles that accumulated in tumors would be visible using mammography within 24 hours. Any nanoparticles circulating in the bloodstream would be too dilute to be seen on a mammogram. When the researchers monitored the nanoparticles for 3 days after injection, they observed that there was wide variability in the amount of nanoparticle that they could observe in different tumors. Some tumors rapidly accumulated signficant levels of the nanoparticle, whereas other tumors showed a slow and low uptake. More importantly, the investigators noted that those animals that showed rapid uptake of the nanoparticles, as visualized using mammography 3 days after dosing, survived significantly longer than did those animals with a slower uptake.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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