
AsianScientist (Jun. 8, 2015) – Professor Subbu S. Venkatraman is currently the Chair of the School of Materials Science and Engineering at Nanyang Technological University (NTU). He is also the founding director of the NTU-Northwestern Nanomedicine Institute, a multi-million dollar research institute that will focus on the medical application of nanotechnology.
What can we expect from the S$60 million NTU-Northwestern Nanomedicine Institute?
We are collaborating with Northwestern University in the US, which is the leader in the area of nanotechnology and in particular nanomaterials. They are putting up a substantial sum of money at their end to co-fund proposals in addition to the S$60 million we are investing.
Most of the work today in nanomedicine including at Northwestern has been on cancer. We are not going to concentrate on cancer because there are a lot of people working in that area. We will work on areas partly to do with the new medical school: cardiovascular, ocular, endocrinological and skin diseases. That’s what will differentiate us. We want to push out at least two projects to the clinic in about three to five years’ time. We want to capitalize on the founding of the medical school with clinician scientists already hired who will be able to conduct the first human studies.
The development timeline for nanomedicine products is currently quite long. And the rate-limiting step is what we call the preclinical phase, which is the phase before you go to human trial. That seems to take anywhere from between seven to 20 years if you look at published literature for established products. We want to shorten that time frame.
As an example we have done this by working with the Singapore Eye Research Institute on glaucoma. It took us about five years to get to the first human study. We want to push that even further if possible. Maybe it’s too ambitious, I don’t know, but that’s the goal.
You are also deputy director of the Nanyang Institute of Technology in Health and Medicine (NITHM). What is NITHM and what are its goals?
NITHM was founded with sort of similar goals, but in different areas, not just nanomedicine. The idea is to have the clinician drive the technology. So until now we have had people working on different technologies that have some application in healthcare all over NTU. These people are working in what I am calling the technology drive mode, meaning that they invent or discover a new technology, not necessarily nano, that has promise for medical applications, but the medical application comes second to the development of the technology. We want to reverse the process, we want the medical need to drive the technologies. So then that means again marrying clinician and technologist at a very early stage in the process.
We have nine programs under NITHM: Sensing and Diagnostics, Therapeutic Medical Devices, Nanomedicine, Tissue Engineering, Systems Biology and Medicine, Medical Imaging and Signal Analysis, Chemical Biology, Health Systems Complexity and Skin Research. Some or all of these will eventually take a life of their own into bigger institutes or bigger funding schemes.
What are your own interests in nanotechnology?
I am interested in two kinds of nanotechnology: one is nanocarriers for drug delivery, gene delivery, vaccine delivery and so on. These are simply nanoparticles of different types that can be manipulated to either target some tissue or to control the release of the drug for long periods of time. The glaucoma product is one example.
In addition, I am interested in the functionalization of surfaces, which means some sort of attachment of nano-entities to a surface so that it has some favorable interaction with the body’s tissues. It may involve integrating the device with the tissue surrounding it, or sometimes isolating the device from the tissue surrounding it. In some cases you might want to protect the device from attack by the body and so hemocompatibility, things that do not clog when contacting blood through the use of some nanosurface modification, is also a major interest of mine. We haven’t solved the problem (of coagulation) yet, but there are some promising avenues we are pursuing.
Where do you see the field of nanomedicine heading? What new drugs can we hope to see in the clinic?
I would rephrase “drugs” to “new systems to make drugs better, less harmful and more efficacious.” Nanotechnology, when it was first applied to medicine they thought it would revolutionize treatment. It was probably a little bit of hype, in assuming that everything when reduced to nanoscale suddenly opens up new ways of treating patients. If you look at the number of approved products in the area of nanomedicine the number is still very tiny.
Trying to target cancer tissue selectively using nanoparticles so that other tissue is not damaged has not had resounding success yet. Can we eliminate completely or minimize the side effects?
Glaucoma is a good example of where I think current treatment modalities are going to change completely. It used to be treated with eye drops, on a daily basis, but older patients sometimes forget to put in the eye drops which can lead to blindness. In a “nano” solution to this problem, it involves an injection that lasts for five to six months and sort of takes the patient out of the equation. This is the kind of pathway we want to open in other areas, in cardiovascular, diabetes and skin research. Using the skin as a portal for nanoparticle drug delivery is where we hope we’ll see some really new modes of treatment in the future.
It is on us to prove that going nano really helps improve matters. So we really must show that nano-sized entities offer substantial benefits to the patient over existing treatments. I think it will happen but it won’t happen for all of the medical conditions; it will only happen for a few select ones at a time.
Some people are concerned about the toxicity of nanomaterials. Is there a real concern here?
We have an effort in nanotoxicology here at the School of Materials Science and Engineering, led by Profs. Joachim Loo and Ng Kee Woei, in collaboration with people from the California NanoSystems Institute at UCLA. The concern is real. The same material in a nano-sized configuration could potentially be a bit more dangerous than the micron-sized case. Cellular entry is also facilitated by nano-size.
For patients who might be treated by injection, for instance, we’ll only study what happens in the blood with these particles as far as patient safety is concerned. But for workers handling or manufacturing these particles, those things can enter the body through many other pathways and so we’ll have to worry about what happens when they go through lung, skin or mucous membranes. When handling nanomaterials, we have to go the extra step to make it safer than micron-sized particles.
Nanomedicine is a cross between engineering and medicine. What are the biggest challenges involved in multi-disciplinary research?
Of course these issues are not restricted to nanomedicine, but getting physicians and technologists together is not always easy. Both tend to be strong personalities; the technologist sometimes believes his technology is so good it will solve every problem in the world and the medical practitioner will say: “Yes, that’s all true but if I end up with a complex way of introducing this therapy to the patient I don’t want it.”
Sometimes, technologies that look great and have good publication records will not be adopted because they are not practical in the final analysis. That’s a big question you have to ask at the beginning of the project, to try to develop something so that the patient will accept it.
Even with the injection I mentioned for glaucoma, fortunately subconjunctival injection already exists for some conditions and patients are used to it. But if it were totally new the ophthalmologists would not be so keen to adopt the technology.
There is a big nanomedicine effort in the United States. How will the NTU-Northwestern Nanomedicine Institute be competitive in this area?
There are groups in the University of California-San Diego, University of New South Wales and Northwestern University specifically concentrating on nanomedicine.
Our approach to differentiate us from the rest is to concentrate on non-cancer treatments and diagnostics. For diagnostics, which is not so cancer oriented, we might for example try to detect infectious diseases using some nano-entities that have biomarkers. That part has already produced some results and there are even some diagnostics kits now available using nanoparticles. Early detection of biomarkers in cardiovascular disease is also something we plan to work on. Relatively speaking, diagnostics are easier to develop and test because you take blood samples and you don’t have to inject it into the patient. So the regulatory pathway is much easier.
What is one area in nanomedicine you would like to make a breakthrough in?
Nanomedicine is a relatively young area and I am personally very excited to be involved in it. I was very skeptical when I first entered the area as I did not think nano would necessarily give a lot of benefits, but I’m now convinced it does.
We have a challenge ahead of us to open new doors, so to speak, in all these various conditions. Diabetes is where my own personal interest would be, basically, if we can mimic what pancreatic cells do inside the body. Not just injecting somebody else’s healthy pancreatic cells into the patient but actually developing an alternative, sort of a protocell concept, that would sense the glucose surrounding the cell and in response to that high glucose concentration trigger the release of insulin from the cells. This is what we cannot do right now, except by using a mechanical feedback device which is bulky and complicated. It would be nice to replace that with a nanosized “cellular device.” That’s one of my dreams.
This article was first published in the print version of Asian Scientist Magazine, Jul 2014.
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Photo: Lester Kok, NTU.
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