Using Nanoscience for Cancer Treatment

Matt McGowan: You’re listening to Short Talks From the Hill, a podcast of the University of Arkansas. My name is Matt McGowan. I’m a science writer here at the university. Today I’m talking to Hudson Beyzavi. Beyzavi is an assistant professor in the Department of Chemistry and Biochemistry. Earlier this year, Beyzavi and his research team published an article in the June issue of Advanced Therapeutics, a leading journal in the field, reporting that they had developed a new drug candidate that efficiently kills triple negative breast cancer cells. Their discovery will help target breast cancer cells directly, avoiding the adverse side effects of chemotherapy. Welcome Hudson and thank you for being here.

Hudson Beyzavi: Thank you very much, Matt, for your time and the invitation.

MM: The study that I mentioned earlier has to do with triple negative breast cancer, and we know that it is one of the most aggressive and fatal types of breast cancer. Could you tell us about this type of cancer, a little bit of background on it, specifically, what does triple negative mean? Why is this form of cancer so aggressive?

HB: Basically breast cancer is the most common cancer in American women with the exception of skin cancer, and currently the average risk of a woman in United States developing a breast cancer at some time in her life is about 12 percent. So basically this is very scary. Therefore we basically wanted to focus on breast cancer, and we have a wide range of type of breast cancer. Some of them are less aggressive and some of them are highly aggressive. In terms of aggressiveness and in the most aggressive side, we have triple negative breast cancer, so depending on the tumor subtype, the applied treatments are different. Depending on the expression of the receptors on the surface of these tumor cells. So, for example, in luminal A subtype we basically have the expression of three types of receptors, known as estrogen receptor, ER, progesterone receptor, or PR, and human epidermal growth factor receptor 2, known as HER2. So for this type of breast cancer that one or two or three of these receptors are actually present, we can benefit from hormone therapy and targeted therapy because we can have a drug which can bind to those receptors so that we can basically treat the patient. However, for triple negative breast cancer, known as TNBC, none of these receptors are present. So TNBC does not respond to any of these three types. That’s why it is called triple negative. So it makes it very challenging actually for any type of… like a targeted therapy, because they don’t have these receptors on them. And also, the not good news is that unfortunately TNBC comprises 15 to 20 percent of all breast cancers. And actually, also in contrast to the other type of breast cancer, the people who get this cancer actually are younger, compared to the other type, and they are usually younger than the age of 50. So that’s another aspect that we really wanted to focus on… this challenging type of breast cancer.

MM: Your lab focuses on targeted photodynamic therapy drugs. Can you tell us what these are, and how they work as an alternative to chemotherapy?

HB: Yes, sure, so photodynamic therapy, known as PDT, is a two-stage treatment that combines light energy with a drug which we call it photosensitizer, designed to destroy cancers or pre-cancerous cells after light activation. So photosensitizers are activated by specific wavelengths of the energy, usually from a laser. And basically the photosensitizers are non-toxic until it is activated by the light energy. And PDT in general is minimally invasive and toxic, so we basically use laser to activate. It generates a very toxic oxygen. We know… we call it a singlet oxygen, which actually kills the tumor cells.

MM: So, you’ve kind of answered this question a little bit, but I would like you to tell us a little bit more about how you attack therapy. How did you modify PDT to attack the triple negative breast cancer problem?

HB: Yeah, so basically I decided to use the other expertise that we have in the field of nanotechnology. So we basically used a new or emerging a class of nanomaterials, metal organic frameworks. So, metal organic frameworks are hybrid material between organic and inorganic chemistry. So we use an organic part, which will be our photosensitizer and a metal cluster, which actually combines these photosensitizers together to build a three-dimensional network, which is crystalline biocompatible. And basically we coated this nanodrug with the sugar molecules, so… in order to target those tumor cells.

MM: How… now this is all happening in the lab, so it’s an in vitro experiment. How did the how did the cancer cells react?

HB: Yeah, so basically we have been studying this for a couple of years, and we actually have tried different materials. So this nanodrug that we successfully published showed the best results. One of the aspects of the anti-cancer drug is that they should be selective. It means they should not harm any healthy cells but specifically the cancer cells, so we always have a control which would be just the healthy cells present. And also we have the different wide range of tumor cells. Actually this drug that we discovered also showed really, really promising results also for cervical cancer. So the way that we basically managed to successfully publish that is, that this drug is highly selective, so you can see that the healthy cells are intact, whereas the tumor cells of a specific interest that we have in this case, TNC, TNBC they were damaged up to like over 90 percent.

MM: You were careful to tell me that we have to refer to this as a drug candidate. Why is that, so why are we calling it a candidate and not just a drug?

HB: Yes, so basically when it comes to the drug development there is a long process of actually about 12 years and is spending about 1 billion dollars on a research project starting from a basic research down to the commercialization. So we have several steps. The first steps would be the basic research and early discovery. That is what actually we have been successful to achieve in the last couple of years here at the University of Arkansas. So we show that the drug molecule works perfectly, as you mentioned, in vitro. In the basically working with the cells. And then the next step is to take this in pre-clinical stage, which means to test them in vivo in animals. So there are actually some studies to make sure about specifically the toxicity of the drug, how the living animal can basically metabolize this, how it is excreted from the body. After the success on this step we need to move forward to the clinical development where we have three phases here. And it’s basically starting with a very limited population of people and then expanding it towards the phase three and after all the successful data. If everything goes well, it will go for the FDA review. So after the final review, then it will be approved for the post-market monitoring and basically going forward to the real drug industries.

MM: Are there other diseases or other forms of cancer that this drug candidate could address?

HB: So we have been also successful to show that our other nanodrug, which is currently being considered for publication, showed great promise for pancreatic cancer. So basically we are constantly modifying our molecule depending on the corresponding receptors and the media of the cancer. I also would like to add another aspect of the drug, that this drug actually is multifunctional, and what it means that not only it is treatment but also because of the metals present, it allows for also bioimaging. So it means we can do the MRI imaging or even a fluorescence imaging to see where the drug actually is located. Because some of the drug that currently people are taking, we do not know where exactly the drug is in the body. However, our drug system not only would allow for the treatment, but we can actually put the patients, for example, at the MRI imaging facility, and see where exactly the drug is located to confirm basically that our targeting has been successful. So not only we are doing targeting by decoration of this drug by sugar molecules and using photodynamic therapy as a treatment to kill the cancers, but also it enables us at the same time to do the imaging via MRI or fluorescence imaging.

MM: Well Hudson, thank you so much for being with us today.

HB: Thank you very much, Matt, for your kind invitation and your time. I really enjoyed speaking with you.

MM: Music for Short Talks From the Hill was written and performed by local musician Ben Harris. For more information and additional podcasts, visit Arkansas Research. That’s arkansasresearch.uark.edu, the home of science and research news at the University of Arkansas.