Pictures of the Future      Fall 2008

The Nanoparticle Toolbox

Interview with Mukesh G. Harisinghani

We’ve been hearing about significant progress in cancer detection and treatment for at least 20 years, yet cancer has stubbornly remained a top killer. Are we finally approaching a turning point thanks to advances in nanoparticle technology?

Harisinghani: Nanoparticle technology holds the potential for becoming a turning point in the early detection of cancer metastases once it enters the clinical arena on a daily basis. As with all cancers, the key question is: has it spread—and the first place to look is in nearby lymph nodes. The problem is that today there is no single noninvasive accurate way of seeing whether a cancer has spread to these nodes—except for iron nanoparticles. When injected, these particles concentrate in functionally normal lymph nodes. They do so because macrophages in normal nodes clear impurities from the blood efficiently. Therefore, any circulating magnetic nanoparticles wind up inside these nodes. This information shows us which nodes are not normal because of their lack of nanoparticle uptake. The next step will be to take nanoparticles that are coupled with a therapeutic payload and inject them directly into cancers. In mice, this causes the particles to be carried to the cancer-affected nodes, which destroys not only the primary cancer, but its early metastases. However, we do not know whether such a process will work in humans.

What are the prospects for combining magnetic nanoparticles with optical probes?

Harisinghani: The prospects are very promising. In the laboratory we can already identify single cells using magneto-optical probes—in other words, a magnetic nanoparticle combined with a fluorescent molecule. Siemens has been actively involved in the basic science behind this development. The company has developed robust imaging systems and is involved in developing the MR-specific workflow processes and associated software. However, there is still a lot to be learned. We have to determine which molecules bind best to which cancers, what kind of light is best for visualizing associated probes, and how close an optical sensor must be in order to see them. These questions are currently in the process of being answered.

Is there such a thing as a molecule that zeros in on any cancer, regardless of location?

Harisinghani: Yes, there is—it is a smart probe—a generic magneto-optical nanoparticle that is activated only by enzymes that are present in cancer cells. This probe was developed here by a team led by Dr. Ralph Weissleder (see Pictures of the Future, Spring, 2007, Interview Weissleder). Siemens funded some of the associated research and is involved in determining how the information can be visualized. Clinical trials on this new probe will probably commence at the end of this year at a medical center in Philadelphia. It will be the very first optical imaging agent of this type to be used in humans. One very interesting result of this is that optical imaging will probably usher in accelerated testing of new medications, particularly in relation to certain breast and prostate cancers. It has the potential to register very early responses to medications in tumors. And by combining it with magnetic resonance tomography (MR), or positron emission tomography (PET)—or both of these methods—we expect that it will significantly reduce the cost of drug testing.

How might such a development change diagnostics and treatment over the next few years?

Harisinghani: Optical imaging will open up the possibility of precise surgical intervention. Pathologies will be visualized and localized using positron emission tomography and magnetic resonance imaging and will then be surgically removed using optical fluorescence assistance. Thanks to this development, it will be possible for surgeons to be more accurate than has ever been the case in the past. What’s more, in many cases, no surgery will be necessary because when the light produced by a fluorescent marker that homes in only on cancer cells goes out following targeted medical treatment, it will provide objective proof that the cancer cells really have been successfully treated. In addition, with variations, this scenario will be applicable to many other diseases and most parts of the body. Nanoparticles are like shells. You can coat them with compounds that seek out unique domains. As a result, it is possible to exploit compounds that bind specifically to cancers or inflammations such as atherosclerosis. Here at MGH, we are working on what might be called a library of compounds. So what does all this amount to? In short, we are developing an increasingly comprehensive toolbox for the early detection and treatment of diseases.

                                                                  Interview conducted by Arthur F. Pease