Nanoparticle reports on drug delivery to breast tumors, predicts response to therapy

Nov 20 2008

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. 

This work is detailed in the paper "Multifunctional nanocarriers for mammographic quantification of tumor dosing and prognosis of breast cancer therapy." Investigators from the Emory University School of Medicine and the University of Texas Health Sciences Center in Houston also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract