 Alright, let's begin. Ask panelists if they have any observations or questions. Dame Julia? It was a fascinating talk. Congratulations. Have you compared what cells you put when you want to construct the blood vessels as a difference between fetal young cells and aging cells? We haven't done that direct comparison, but looking at other work in the literature, there has been a small amount of work looking at fetally derived cells or brand new neonatal cells, and a difference between that and what we see in adult cells is related to the assembly of elastic lamina. So you see elastic in both vessels, but you see the assembly into very organized structures just if you're using the very young cells. Any other questions? How far from clinical application? The engineered blood vessels, I would say, still several years, especially the tissue engineering industry has gone through a rough period and the nanotechnology for cancer, the clinical trials are imminent now. A couple of questions from the audience. You use gold nanoshells. Can silver be used as a coating? What would be the comparative advantages or disadvantages? We actually can make materials with silver. When we make them with silver they give us the ability to go to gain optical properties a little bit lower down into the UV ranges even. One of the issues is that the silver coatings are less stable in the biological environment and are not horribly toxic, but do have a slight toxicity associated. Would nanoshells be used to fry cancer cells rather than radiation thereby causing fewer radiation related side effects? That is our hope. We're not quite trying to fry them. We're trying to get a temperature change of only about 15 degrees C. If we get too hot you will start to cause damage to surrounding tissue because the heat has to radiate out. But if we go just for the threshold of the heating we need to destroy the cancer cells then we can have a very, very small damage zone to the surrounding normal tissue into where we're really at the single cell level of controlling where the damage occurs. Is this procedure going to be applicable to all solid tumors? Hopefully. At this point we think so. We've done animal studies in a number of different cases but not quite enough to agree with the word all. For example, would it include brain tumors as well? Yes, we've done both glioma and medulla blastoma models orthotopic and have had very nice results there. Could your nano-image be used to look at engraftment of your contrast in vivo? Potentially. We haven't tried that but I think it would be possible. Just sort of a practical question. Who funds your research, your public or private? Who owns the patents for the hydrogel or other materials? Okay, so my last slide actually did have the funding agencies. So a number of federal agencies, NIH, NSF, interestingly DOD actually funds a lot of cancer research. They have a congressionally directed medical research program that is targeted for breast cancer, for example. We have some funding from there. We have some from private foundations. We have a very small amount from some corporate sources. And the patents, as part of my employment with Rice University, they are the owners. Okay. Here's another question I think a number of people would have. What happens to all the nano-shells that you inject into the body? I'm so often asked this question. I should just start addressing it in the talk. So we designed them to actually be too large to be filtered through the kidneys. Our first generation were smaller nanoparticles and they clear from the body too quickly if they can go through the kidneys into the urine. But if we make them large enough, they can't do that. And then instead, they're gradually cleared through the liver. So they're taken up by macrophages over time. They eventually go to the liver, are excreted into the bile duct. And over a period of two to three weeks, you can detect them coming out the end of the digestive system. You mean it lights up? In the infrared. Another question here. In the repair of, for example, damaged hearts, which therapy do you think will be first to market? Stem cell repair of damaged muscle or embedding of nanoconstrictors in damaged muscles? I would probably bet on the stem cells that are already into clinical trials. And I think that the ability to really get that much control over nanomaterials is probably still a decade away. Please help me visualize the cell sizes that we're dealing with here. So an average human cell is on the order of about 10 microns. And I don't know if this is so relative to the nanoshell. So the nanoshell would be about three orders of magnitude smaller than that. So trying to visualize a good difference between a human cell. How about with regard to the width of a human hair? Anyone remember how wide a human hair is? Off the top of my head, I think I remember 100 microns. Something like that. So your average cell would be at 10 microns. 80,000s of a diameter of a human hair. The other question that comes to mind when I hear that, you talk about attaching antibodies to these nanoshells. And you make it sound really pretty easy. What's involved in this? I mean, how long does it take? Do you have whole platoons of graduate students that are spending most of their life doing this? Or is it completely automated? There is that platoon of graduate students. I had a picture of them on the last slide, too. It is rather a platoon, although the actual attachment is quite easy. So gold nanoparticles have actually been in use since about 1970 as ways to detect specific structures under electron microscopy. So they're very electron dense, so you can see them. They can light up places in tissue under the electron microscope. And so people have spent decades now developing very robust techniques for attaching antibodies onto gold, and we were able to just come in and capitalize on all that work. To what extent have the nitrous oxide releasing hydrogels been used in clinical trials? And have they compared with other treatments such as drug eluting stents? They have not yet been used in clinical trials. One of the manufacturers of drug eluting stents is now starting to do a comparative study between our materials and drug eluting stents. And so hopefully in about six months we'll have a good answer for that. Are you worried about the financial involvement of this company and one of the technologies influencing the results? My sense is that they've recognized some problems with the technology that they have and that they're trying to find a new option for their next generation. Could photothermal ablation be used to bind nanoballs to ischemic tissue and kill them and therefore stop heart arrhythmias? Potentially. So any tissue structure that you could specifically recognize and cause binding to, you could wipe out. And so aside from cancer we've also had some interest in looking at diabetic retinopathy where you have overgrowth of blood vessels in the back of the eye that have specific markers you can recognize. There are many different diseases besides cancer that this may be applicable in. And along that same line, can nanoshells target non-solid tumors? We don't know. We have not looked at all at things like leukemia yet. I think it would be very interesting. I think there's some potential but we have not done any studies in that area yet. So why are the nanoparticles not recognized by our immune system? So the immune system has evolved to recognize biologically oriented molecules. The surface are very inert. When we're attaching the antibodies we actually have a coating of PEG while we're putting the targeting antibodies on. Polyethylene glycol or PEG is actually a compound that's added to many materials to prevent interaction with the immune system. So that helps as well. How small does the nanoparticle have to be to cross the blood-brain barrier? In areas where you have tumor growth you actually have a lot of disruption of the blood-brain barrier. And so we see them crossing into tumor regions when they're around 100 nanometers or smaller. In normal regions they're not crossing those blood vessels. Are you essentially shutting down the enzymes in the cancer cell with the heat change, thus killing them? The main mechanism for cell death actually seems to be permeabilization of the membrane. So very quickly after the light treatment we see that the membranes become very leaky and cells you normally keep a very different composition as far as the fluid inside the cell versus outside the cell. When the membrane stops functioning and you have substances able to cross that's actually fatal to cells. And that seems to be the main mechanism although certainly the heating would be disrupting protein functions as well. Do you anticipate or is it now possible to use the Raman biosensor to detect or diagnose in vivo infectious organisms? Yes, we think it should be. So we can definitely do it in blood samples and we know that this wavelength of light crosses through tissue so we think that it would be possible to do detection in vivo. One final observation here and I'll have to admit I get this just about every year. There's much talk of how few women there are in science. I see four of your collaborators are three women and many women students. Congratulations. Well, I think this will conclude our second day of talks here. I'd like to offer a couple of thanks here. One is I would like to offer my thanks to my colleagues here at the college. When we put this conference on it seems like everybody at the college takes a couple days out of their normal life and devotes it strictly to making sure that everybody comes here has a good time. And I would really like to tell them how much I appreciate their willingness to do that. And then I would really like to thank our panelists for giving us two days of absolutely brilliant talks. You're getting a standing ovation, ladies and gentlemen. I think you should rise and acknowledge it. Thank you very much for coming. Our banquet this evening will start at 6.30. I would expect that Dr. Miles' talk will begin about 7.30. If you do not have a banquet ticket, we will be simulcasting this in Alumni Hall. Probably beginning about 7.30, I should say. Thank you again.