In an attempt to create a single device that can image and treat tumors simultaneously, researchers at the University of Texas Southwestern Medical Center at Dallas have successfully melded magnetic iron nanoparticles, the anticancer drug doxorubicin, and a polymer tagged with a tumor-targeted molecule into a stable nanoparticle that accumulates inside human tumor cells. These nanoparticles are detected using magnetic resonance imaging (MRI) and release their drug payload only inside the acidic environment of a tumor cell.
Jinming Gao, Ph.D., and David Boothman, Ph.D., led the team of investigators that designed the biocompatible, multifunctional nanoparticles to target a protein known as ævß3, which is found on many tumor cells and on the blood vessels that develop around tumors. The researchers reported their findings in the journal Nano Letters.
The investigators formed the new nanoparticle by first combining 8-nanometer diameter iron oxide nanoparticles and doxorubicin with a polymer known as maleimide-terminated poly(ethylene glycol)-block-poly(d,l-lactide). When these nanoparticles self-assemble, the maleimide chemical group sits on the outside of the particle and provides an attachment point for a tumor-targeting molecule. In the current work, the investigators used a small protein known as cyclic-RGD, which binds tightly to the ævß3 protein and triggers a process that carries the attached nanoparticle into the cell. Once inside the cell, the particles act as potent MRI contrast agents that pinpoint the location of those cells.
An important distinction between tumor and normal cells is that the former are more acidic inside than the latter. Not coincidentally, the polymer that the researchers used to make their nanoparticle falls apart when subjected to such acidic conditions, releasing doxorubicin inside the cancer cell. Cytotoxicity studies showed that these multifunctional nanoparticles are highly toxic to tumor cells growing in culture. Currently, the researchers are testing the ability of these nanoparticles to locate and treat tumors in animal models of human cancer.
This work, which was supported by the National Cancer Institute, is detailed in a paper titled, “Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems.” This paper was published online in advance of print publication. An abstract is available at the journal’s website.