Hybrid metal and organic nanoparticles for targeting, imaging, and treating cancer

Using a set of three biocompatible polymers and a nanoparticle containing gadolinium, a team of investigators at the Colorado School of Mines has created a nanoparticle platform that has the potential to target, image, and treat cancer.

Gadolinium ions are used widely in medical imaging because of their ability to dramatically boost magnetic resonance imaging (MRI) signals. However, gadolinium can be toxic, particularly to the kidneys, so researchers have examined numerous ways of creating gadolinium constructs that would shield this element from the body.

Writing in the journal Biomacromolecules, a team of investigators led by Stephen Boyes, Ph.D., solved this biocompatibility problem while creating a versatile nanoparticle, platform-attaching tumor-targeting molecules, and therapeutic agents. The investigators started by creating gadolinium nanoparticles in which the gadolinium ions were stably constrained with an organic framework. Next, they grew a three-component polymer on a nanoparticle surface using a chemical process known as reversible addition-fragmentation chain transfer (RAFT). The resulting polymer coating proved in tests to be both biocompatible and highly stable. In addition, the coating contained various chemical groups that enabled the researchers to attach the anticancer agent methotrexate and a tumor-targeting peptide known as GRGDS. The researchers note that they could have chosen other targeting and therapeutic agents to attach to the polymer coating.

MRI experiments showed that these nanoparticles generated magnetic signals as strong as those produced by MRI contrast agents now in clinical use, but with one-third less contrast agent. In addition, the investigators showed that one of the polymer components produced a significant fluorescence signal, suggesting that these nanoparticles could provide clinically useful, dual-mode imaging capabilities. Tests with tumor cells grown in culture showed that these nanoparticles were effective at targeting tumor cells, with little uptake by normal cells. Once taken up by tumor cells, the nanoparticles were as effective at killing the cells as was methotrexate.

This work is detailed in the paper "Polymer-modified gadolinium metal-organic framework nanoparticles used as multifunctional nanomedicines for the targeted imaging and treatment of cancer." Investigators from Colorado State University also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract