Dendrimers are spherical polymer nanoparticles that have shown promise as targeted anticancer drug delivery vehicles. Iron oxide nanoparticles have already demonstrated the ability to image tumors and metastatic lesions.
Now, researchers at the University of Michigan have combined the two, producing a layered nanoscale construct that targets and images tumors in animal models of human cancer.
Reporting its work in the journal Advanced Materials, a team of investigators led by James Baker, Jr., M.D., who heads 1 of 12 NCI-funded Cancer Nanotechnology Platform Partnerships, created its nanoparticle construct with the aim of targeting iron oxide nanoparticles to tumors. Previous attempts to add targeting molecules directly to iron oxide nanoparticles have had limited success because the resulting nanoparticles were not stable in the bloodstream and were removed quickly from circulation by immune system cells.
In this study, the investigators' first attempt at linking dendrimers to iron oxide nanoparticles was successful, but the resulting nanoscale construct accumulated largely in the liver rather than in tumors in test animals. Further investigation suggested that this construct was not stable in the body. To remedy this problem, the researchers first coated the iron oxide nanoparticles with multiple thin layers of two different polymers, poly(glutamic acid) and poly(l-lysine). Next, they added a layer of dendrimers that contained the tumor-targeting molecule folic acid and a fluorescent dye. Then, in a final step, the investigators chemically linked the multiple layers to one another, creating a stable shell of dendrimer and polymer on an iron oxide nanoparticle core.
Tests using both tumor cells growing in culture and in mice with human tumors showed that this new construct bound specifically to tumor cells that overexpress a receptor for folic acid. MRI was able to easily detect tumors in mice. MRI studies also showed that the hybrid shell-core construct accumulated far more in tumors than in liver, kidney, or spleen.
This work, which was supported by the NCI's Alliance for Nanotechnology in Cancer, is detailed in the paper "Dendrimer-Functionalized Shell-crosslinked Iron Oxide Nanoparticles for In-Vivo Magnetic Resonance Imaging of Tumors." There is no abstract available for this paper, but a citation is available at the journal's Web site. View citation