Developing Nanoparticles to Image, Target and Treat Cancer

         

Feb. 19, 2009 — Scientists at the Siteman Center for Nanotechnology Excellence have spent years researching nanoparticles and investigating their use in the fight against cancer. Their research, focused on using the complicated microscopic particles to find and attack tumors before they're large enough to be harmful, has led to a clinical trial to study the futuristic-sounding technology in humans.

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TRANSCRIPT OF AUDIO FILE

On this edition of Cancer Connection, we will talk about nanotechnology, what it is and how the research will be translated from bench to bedside.

Host: Thanks for downloading this podcast from the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St Louis. I’m Jason Merrill. Nanotechnology is defined as the development and use of materials and devices to manipulate matter at the level of molecules and atoms. For the field of medicine, this has very promising ramifications. In St Louis, the Siteman Center of Cancer Nanotechnology Excellence at Washington University, in collaboration with the University of Illinois at Urbana-Champaign and the Alvin J. Siteman Cancer Center, provides a research and clinical resource in the Midwest for both the fundamental exploration of nanotechnologies applied to cancer and also their translation, commercialization and application in the clinical environment. Funded by a five-year, $16 million dollar grant from the National Cancer Institute, the center fosters integration among the physical, biological and clinical sciences and is an interdisciplinary effort designed to move nanomedicine research forward. The director of the Siteman Center of Cancer Nanotechnology Excellence is Sam Wickline, and he is here to talk with us. Dr. Wickline, thank you for joining us.

Wickline: It’s my pleasure to be here and talk about nanotechnology.

Host: Well, let’s start at the beginning. How do you define nanotechnology?

Wickline: Nanotechnology is the study really small things. These things are smaller than a red blood cell that floats around in your bloodstream and supplies oxygen. These are at least 10 times smaller in diameter than a red blood cell and are generally considered to be smaller than somewhere between 100 and 300 nanometers. These definitions have been developed by a variety of scientific organizations so that we can focus on these very small agents that can be used not only for commercial applications – for example, coatings on your clothes to prevent stains, which are very commonly used – but also to define new structures that we can make that will be compatible with the human body to improve health care.

Host: The small things that you are looking at in nanotechnology focus on treating cancer and heart disease. How far have you come since you started doing your work?

Wickline: So this whole area got started some time ago. In fact, for us, we started in about 1994 looking at new nanostructures that could both be used for identifying cancers and heart disease and also for treating cancer and heart disease. These agents can be used not just for imaging – for example, if you’re trying to find very small tumors or vascular plaques that might cause heart attacks and strokes – but the same nanotechnologies can be used to carry drugs to those exact sites. So from 1994 to 2008 or 2009 is at least 14 years for us, and over this period of time, we have developed several companies in the area that are charged with taking these kinds of nanotechnologies into clinical trials. In fact, we have come as far as now initiating clinical trials with nanotechnologies that are meant to find small cancers and heart disease.

Host: Talk a bit about those. Your work has come up with at least one treatment plan, and you have a human clinical trial on the horizon studying blood-vessel growth. What are some of the things you’re researching?

Wickline: One of the problems that cancer causes is the tumors that you get often don’t grow. They sit around for a long time, and no problems come of them. But then occasionally they will begin growing very quickly, and they need a blood supply to do that. The blood supply that they call in to help them grow and then metastasize, or spread, is the blood supply from your own body. And they command blood vessels to help them do that.

The nanoparticles that we have are meant to seek out these new blood vessels that support the growth of tumors. We’ve targeted our nanoparticles directly to those tumor blood vessels. This occurs at a very early stage. So if you have a very small tumor that’s not growing very much or is indolent, or hidden, if you will, when it starts to grow very fast, it needs these blood vessels. This is the point at which we would like to find these blood vessels because that’s the point at which the tumor becomes dangerous. So we can target blood vessels for imaging, or detection by imaging technologies, with nanoparticles that adhere to these blood vessels. And we can also simultaneously give drugs to wipe out the blood vessels, which will then control the tumor growth.

The same thing holds true for cardiovascular disease. The plaques – or the hardening of the arteries, if you will, that grow on the blood vessels around your heart – need a blood supply in order to grow. So we have the same problem that we have in cancer, where the blood vessels are critical to the growth and enlargement of these plaques that cause heart attacks and strokes. We can now target these two very different kinds of pathologies with the exact same nanoparticle.

Host: So how do you see this research going from bench to bedside?

Wickline: The role of nanotechnology and medicine has come full circle now to the point where this was a laboratory exercise eventually going into animal models of cancer and cardiovascular disease to now being in clinical trials. This is a very complicated technology compared to standard medications that would go into clinical trials, for example, small molecules or chemicals that you might take to reduce cholesterol or agents that you might take to treat a tumor. These are much simpler in their form and in their clinical trials then the materials that are made from nanoparticles or nanotechnologies. This is because the nanosystems that we use have a lot of moving parts. They have a particle that’s small. They have a targeting entity, which enables them to find things that you want them to find. They might have an imaging agent on them so you can see them with a magnetic resonance imaging or a CAT scan. And they might also have a drug on them, which is the only thing you usually would get if you had a cancer chemotherapeutic agent.

So you can see the multiple components make these agents – nanoparticulate agents – very challenging. And the regulatory requirements for moving them from the bench to the bedside are much more complicated than standard chemotherapy agents or standard agents that would treat heart disease. So the real issue for us is to satisfy all of the requirements of the Food and Drug Administration to ensure safety of these agents. We have done that in the case of the nanoparticle that is now targeted to blood vessels around tumors, which is now in clinical trials for imaging small tumors.

Host: This work really could change the standard of care for patients, couldn’t it?

Wickline: Yes. We believe the most important thing about nanosystems is that they can carry a large amount of drugs directly to the site without putting the drugs in unintended sites. So, for example, many of the chemotherapeutic agents that you use also have side effects on other organs that are normal, and you don’t like that to happen. So what you hope is that in the case of standard chemotherapeutic agents, the effect on the tumor is much greater than the effect on the normal tissue. And that margin is what you’re looking for in order to treat a tumor.

In our case, we’re going to use a very small amount of the drug and count on it being delivered directly to the tumor site for its action there and it being cleared out of the body and other sites so it won’t harm normal tissues or normal organs. We hope the therapeutic effect is greater because we’re targeting it directly to those tumors that we find and image. And we hope the side effects are lower because we’re going to use a very small dose and have it accumulate at the site it’s intended to reach. So in fact, what we would gain from this kind of targeted nanoparticle technology is a lower set of side effects and a higher local therapeutic efficacy.

Host: Is there anything else people should know about nanotechnology?

Wickline: I think one issue that always comes to the front when we begin talking about a novel technology is its side effect profile and its toxicity profile. Nanotechnologies are already approved in clinical medicine, for example, in the treatment of cancers with drugs like Doxil, which basically are nanoparticles that carry drugs. They’re just not targeted, and they’re not used for imaging. So these are already in existence and in clinical medicine and approved for use.

The real issue with any drug, nanotechnology notwithstanding, is to make sure the agents you’re using are safe for patients or safer than other agents that have been used in the past, comparative agents. So we go through great pains to make sure that these agents are not toxic to other organs, that they deliver the drug where they’re supposed to deliver it and that the effect is magnified by having a targeting system on these nanoparticles. So really it’s no different than proving the safety and efficacy of any other drug. There’s nothing particularly special about that. You just have to design them so that they’re safe for human beings according to the FDA requirements.

Host: Dr. Wickline, thank you for joining us.

Wickline: It was my pleasure.

Host: For more information about nanotechnology, you can visit the Siteman Cancer Center online at www.siteman.wustl.edu or call 800-600-3606. Thanks for downloading. Until next time, I’m Jason Merrill.