Nanoparticle research target moves from terrorism to cancer

Fighting bioterrorism was what Raoul Kopelman had in mind when he and collaborator Martin Philbert first conceived of the minuscule beads he calls nano-PEBBLEs. Eight years later, his nanoparticles are engaged in a different sort of battle, against the deadliest type of human brain cancer.

(Photo courtesy Raoul Kopelman)

Along the way, Kopelman's concept of nano-PEBBLEs and their potential has gone through some major shifts, a saga he will relate in a Distinguished University Professorship lecture at 4 p.m. Jan. 16 in the Rackham Amphitheatre. Kopelman, who is the Richard Smalley Distinguished University Professor of Chemistry, Physics, and Applied Physics, likens the current generation of nano-PEBBLEs to "remotely controlled artificial viruses."

That's a shorthand way of expressing the qualities described by their full name: nano-Photonic Explorers for Biomedical use via Biologically Localized Embedding. The tiny particles are polymer spheres, typically 20 to 200 nanometers in diameter (about the size of a virus), and in early incarnations were used simply as sensors to explore and monitor cellular processes.

Now their jobs are much more demanding, but the PEBBLEs are up to the task, thanks to their ability to carry an assortment of molecules, both inside and upon their surfaces. Some of these molecules selectively guide the nanoparticles to their cancer-cell targets inside the body, some control the time nanoparticles spend in the bloodstream, some enhance tumor visibility on MRI images and others deliver knockout punches to the cancer cells when triggered by exposure to light.

Nano-PEBBLEs offer many advantages over traditional chemotherapy drugs, Kopelman says.

"The really bad cancer cells get immune to chemotherapy drugs—they pump the drugs back out," he says. Cancer cells can't do that to nano-PEBBLEs. Another advantage: The "killer oxygen" that nano-PEBBLEs deliver to cancer cells, setting off an avalanche of damage, is too unstable to wander off and damage healthy cells, so only targeted cells are affected. Including molecules that make nano-PEBBLEs more visible in MRI images provides an added bonus, helping to show where tumors are located and how they respond to treatment.

In research just published in Clinical Cancer Research, Kopelman and collaborators Brian Ross and Alnawaz Rehemtulla from the U-M Comprehensive Cancer Center and Martin Philbert of the School of Public Health have demonstrated that drug-laden nano-PEBBLEs can be highly effective in treating the virulent brain cancer 9L-glioma in rats.

"This is the first time that this deadliest form of human cancer has been cured by any existing therapeutic approach, though so far only in rats, and only in about 60 percent," Kopelman says. "More research is still needed."

Another significant achievement of this collaborative project, led by Kopelman and supported by a $12 million contract from the National Cancer Institute, is work published recently in Advances in Drug Delivery Research showing the nontoxic nature of these therapeutic PEBBLEs, as well as their natural elimination from the body.

Currently, Kopelman also is engaged in a collaborative project with Roswell Park Cancer Institute in Buffalo, N.Y., using similar nano-PEBBLEs, which he calls "magic nano-bullets." Used as sensors, nano-PEBBLEs continue to give a better understanding of the basic biochemistry and biophysics of cells.

In particular, "nano-voltmeter" PEBBLEs have unexpectedly shown extremely high electric fields throughout living cells. Kopelman also is using magnetic PEBBLEs to detect individual bacteria and their growth rates, with the aim of shortening lab tests for undiagnosed infections from one week to one hour.