By: Jennalynn Fung, PharmD candidate c/o 2025

Dr. Hyunah Cho, Ph.D., an Assistant Professor in the Department of Pharmaceutical Sciences, was awarded a $745,000 R16 Sure-First grant from the National Institute of General Medical Sciences (NIGMS). Her research is focused on developing nano-based optical imaging agents as prospective tools for brain imaging.

If applied clinically, they would improve tumor resectioning in brain surgeries by enhancing visual distinction of cancerous tissues from normal tissues, thus increasing surgical accuracy and precision, and lessening likelihood of iatrogenic injury. This innovation would provide surgeons the ability to more completely remove cancer from the brain, thus improving surgical outcomes, cancer remission rates, and patient survival.

The imaging agents are composed of a fluorescent particle attached to a targeting moiety, which will drive the entire chemical compound towards a targeted tumor site. The fluorescence will become activated (or “turn on”) at the site of the tumor. Dr. Cho compares this to a candy which contains a fluorescent agent at its core – it remains inactive, until it arrives at the tumor, in which it breaks apart and releases the fluorescence – enabling surgeons to identify the tumor as glowing tissue more easily.

As an assistant professor, she has many students who are interested in working in her lab and has lots of advice for them when it comes to pursuing research. One of those tips is being realistic and understanding that 99% of research projects fail, and if they succeed, it takes much longer to directly reach the patient. All things considered, the research that Dr. Cho does today on nano-based optical imaging agents with the NIH grant may be just the beginning of biotechnological advancements that can benefit people around the world.

Q&A

1. Can you walk us through the inspiration behind your research on nano-based optical imaging agents for brain tumors?

Many cancer patients often have surgery because surgery is a primary regimen to treat cancer. Greater than 50% of patients come back to hospitals because tumors regrow or metastasize somewhere. So, if there’s a way to help surgeons to make better resections the first time so we can minimize them coming back for another surgery, start thinking about contrast agents and visualize the tumor better. The contrast-based agent is fluorescent dye in polymer brain cells, and this is engineered to target brain cells. This imaging agent will paint the tumor. Surgeons wear surgical goggles, looking into the patient they might see colors coming from the tissue. Oftentimes, tumors may not be distinguished. Can look like fat or surrounding tissue, but making a clean cut is difficult, especially the brain. Tumor or lungs you might scoop more to remove as much tissue as possible and that’s safe but not with the brain, that is lethal. Because of this, it is important to show which is real tumor tissue and which is not. Using optical imaging, surgeons can have another tool. They can use their naked eye to remove it, and then use the goggles and recut if they missed anything. This ensures they can keep as many surrounding brain cells as possible that are normal.

2. Can you explain in simple terms how the fluorescence signal ‘switches on’ when it arrives at the tumor site?

Think about like a candy, see something in the middle of the candy, deliver the whole candy to the tumor tissues when the fluorescent agent in the candy, it is aggregated not showing the fluorescent signal, but once reaches the tumor cells, the candy breaks apart, the agent incorporated in the center will slowly come apart and will show much stronger fluorescence. Before they reach the tumor they show nothing, but once they reach it will break down at the tumor site and the fluorescence comes out.

3. Why does the candy only break down at the tumor site?

Attached to a targeting moiety, so it can be decorated with something else. The targeting moiety will shoot to the tumor and will then break, and the micelles will open.

4. Is fluorescence a novel method?

People have tried to show fluorescence from the beginning. But most studies, people tried to deliver something with strong fluorescence immediately. However, the signals are strong, and it can go to other locations like the liver or kidney. I am one of the few who adopted the approach of trying to use this system intranasally. Through olfactory system, it will go to the brain. I don’t see anyone else doing the intranasal route for the imaging, and that was one of the positive comments I got from NIH grant. They commented this as a high risk, high reward with intranasal delivery of the agent, especially for brain cancer. This can be exciting because if it works, it can open up a lot of new areas to study.

5. How do you think nano-based imaging technologies will change the landscape of brain surgery in the future?

The good thing about nanoparticles is that it can be used for different cancers and different organs. It can also decorate the nanoparticle surface with different peptides and antibodies. Antibody A will go to the liver. Antibody B will go to the brain. So, it depends on the site of action you expect. Because of this, you can really increase the specificity of the drug and decrease the side effects. When something is not targeted, it will go to the entire body and can hurt your hair follicles, your skin, and different organs. For example, chemotherapy patients will lose their hair and experience different side effects, because the drug goes everywhere. With nanoparticles, we can change the targeting and reduce side effects.

And with nanoparticles, you can make liquid form of the poorly soluble water drugs, and many chemotherapeutic agents are poorly soluble. But you still want to do injections, so you need excipients. This can cause allergic reactions. With the nanoparticles, you can just add poorly water double drugs. Like putting it in the candy, and it will be hydrophilic. This way it can dissolve water and improve water solubility, but you don’t need to add any excipients or alcohol. Often, you would need to add alcohol to add more drugs to the excipients, and alcohol is toxic. But with nanoparticles, you don’t need those toxic excipients.

6. In your view, what are some of the current gaps or limitations in brain imaging technologies that your research addresses?

I am interested in nanoparticle development. This one of my few nanoparticle projects. Nanoparticles with natural ingredients like soybeans can incorporate hydrophobic or poorly water-soluble products and turn it into lotion or serum. That can be one of the projects, not too serious, more of a consumer product and more about consumer care. Other nanoparticle projects I want to visualize are for Parkinson’s Disease, Alzheimer’s, and ovarian cancer. This is a platform that depends on what drugs you have, agents, and targeting moiety. You can apply it to so many different areas. Nanoparticles was one of the things done in my PhD program, my thesis project. To me, it is an exciting time that people know how important nanoparticles are now!

One of the main issues with brain imaging, or imaging in general, is that in order to use fluorescent imaging, it must come with detection tools. So, you need a monitor and microscope that can really visualize the fluorescence. This can be challenging, especially when used simultaneously in a busy operating room, and may not be acceptable to surgeons who are operating at the same time.

The specificity–how do we guarantee how much of the nanoparticles and contrast agent actually goes to the tumor? Is it going to go 100% to the tumor or go to a different organ? Will the surgeons see it? Given how difficult it is to cure brain cancer, I think the future is bright. People will be willing to adopt and explore new and different techniques and modalities to help the surgeons.

7. What are some of the ethical challenges or considerations that come into play when developing these kinds of imaging agents for brain surgery?

Some challenges include using animal subjects and cancer cells, or performing in vitro work. We don’t file an IRB. For animals, we need specific approval to get certain protocol approved. So we can execute animal studies with certain doses, dosing regimens, how we deal with animals if they are sick, when do we stop the animal study. Losing 10% of the body weight, they might be sic because of the cancer, because of the doses, there might be different reasons, so you have to be ethical. Sometimes want to do research and see the result, but the animal is getting sick, you have to top it. But sometimes have those tempting to continue, just one more day, maye there is results. Treat the same as a human subject, treat the animals with human respect.

Ethical way to sacrifice animals. Brave new world. Have to make sure you’re not violating it. Animals experience pain and uncomfortable feelings, and have to make sure you’re not going above what they can handle.

8. What was the most challenging aspect of securing the $745,000 R16 Sure-First grant from NIGMS?

Very difficult. Most of the faculty members not just school of pharmacy, everyone competes for the same award. There is fierce competition, most of the time faculty members need to apply over and over. It is difficult to get first trial, but i was lucky that i got it first time. It is very difficult. You apply, frustration comes, review the reviewers comments. There are nice ones, but many are rather negative you need how to deal with the negative comments and improve your proposals. These awards are pretty high in terms of funding, the money, so everyone wants to get an award, everyone wants a better research environment. Many times we assume we are not going to get in. 50% of me imagines that we will not get the grant. There might be people with more resources, students, so competing without knowing who else is entering, it is very difficult, federal funding from NIH and NSF. one of our goals is always to secure the funding.

Once you secure the funding, it will open up so many opportunities. I can support my students, get the supplies they want. Before i secured the grant, I don’t have enough funding. Sometimes they want to order more pricey supplies or animal studies, but I don’t have funding to support it. But now I do. So now my students are very happy. So they don’t have to look for something to borrow, they can just stock up. This award involve intense animal studies and expensive supplies and ingredients and a number of animals, so without securing the NIH grant, I wouldn’t be able to conduct any of these studies. This will help me do more top notch research projects and publish papers in high impact journal. Get to work with more undergrads and Pharmd students. And the fact that I work on this project, it is public information that I secured the grant and a brief summary of the grant, I get to work with people outside of the school. They know what projects I have done. I have received some emails from companies or others outside, and they asked if we can collaborate.

9. How do you stay motivated and passionate about research, especially with the challenges that come with innovative projects like yours?

Part of what motivates me is working with students, undergrad and graduate. They bring their own ideas and they got exciting results to share with me. Seeing them excited about research and digging in the details, to learn about the project, that’s one of the motivations. I want to be here to motivate and support them to become researchers and scientists. Second is when I come up with an idea, a hypothesis. Will it really work? After the experiment I can confirm that my hypothesis is correct, that this is applicable to the real world, this is what I was thinking, and it is really true. It is very motivating;

Academic research is difficult to get on market, unlike findustry research projects which are highly likely to be commercialized and will reach the patient. For us, it takes longer and it is unfortunately unlikely that it will immediately reach the patient. But, I can see that what I publish can help others. I published a paper about rectal suppository of Artesenate, and found it was talked about in one of malaria association website, and that this is possible and this is the latest research so my academic research can be spoke about by physicians and healthcare providers and the potential work and this motivates me to do more.

10. How do you balance your teaching responsibilities with your extensive research work?

Since I have the federal grant, the federal grant guarantees your teaching workload relief. Teaching 1 course less. I was supposed to teach 2 compounding classes, now just teaching one section and can spend more time doing more research. This is a benefit of the grant; you have more time spent on research and training students.

Not my first time teaching compounding classes, so not spending too much extra time to prepare for teaching. Course notes spent less because she already spent a lot of time in the beginning. It is a good balance because she has more time doing stuff in the lab.

11. How do you decide which students to add to the research project?

This is for graduate students, but I’m also thinking that I want to include PharmD students and undergrad students. I always try to have as many students as possible. Usually, students reach out through email. They learn about my research through my classes. Some students they present things about their research at the symposium, or women in science talk. Students often think research is having good results, but 99% of the time we fail and figure out why we fail. So, I’m frank with the students that this is not always the reality, not always butterflies and flowers. You may spend a lot of time with the process, coming after class to run the experiment. I explain to them what goes into the research. Starting from small tasks, I want to have one or two undergrad students working on this task, would you be interested in doing so. I do a casual interview with them, explain the research, the lab, how we go about doing the research, then compare their schedule, willingness to time, and want them to spend 1 year in the lab.

I want them to see from beginning to end and write a paper or an abstract to present with me. If they meet all of those requirements, I will select the student. Also, about chemistry not about GPA not about extracurriculars, I just want to see if that student will match my level of excitement we will be sitting down and talking a lot so I see a few different elements and how many positions I have and including students. This grant work hasn’t decided on how many students to have, but I’m hoping to have 1 or 2 undergraduate students to assist graduate students and in writing abstracts and writing papers together. I really want our undergrad  students and PharmD students to be exposed to research. If you don’t know what it is, you wouldn’t really think about that area at all. Research can be frustrating, but really exciting and what you learn in the classroom can be explicable, so I want to share the knowledge and experience as much.

Around the time I had to graduate, I was thinking about career options, explored, went to seminars and webinars. I remember one of the talks done by faculty members was talking about injectable products, NDDS (novel drug delivery systems) products, nanoparticles, and so I chose a research rotation. He gave me so many opportunities, I really enjoyed it so much. I got to attend meetings outside of school and got to present research at ASHP. It is very rare for undergrad students to go and present, that was eye opener. I didn’t know about all of that amazing research, people from the industry and academia. So, when I came back, I decided to do a masters and PhD. That was how I began to thinking about my career path in science and research.

12. What advice do you have for students who are interested in pursuing research in pharmaceutical sciences?

I am always telling students if they are interested in doing research that they should read and see what type of research they’re interested in, and what faculty members can do. Just going through their bio or going through the St. John’s website helps. This describes what research they do, what papers they have published. They can actually go to those papers and go through those and see what they are more interested in so they can narrow down the faculty members or labs in and outside of St. John’s. Visiting the lab, making an appointment to see it, asking to shadow to see if there are no positions open. They can be more proactive, reach out to more faculty. Also, if they are truly interested and have certain ideas, they can suggest it to professors. Some students suggest it, it happens to me, and that can be an interesting collaboration. It can be a win-win situation because students can execute their own ideas and the professor might not have thought about it. All the faculty are truly excited to have students work with them. So just do a little bit of research and contact them, get their feet wet and see what they like the most. Can discuss their future career if they’re seriously thinking about that so faculty should be able to advise.

Published by Rho Chi Post