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“Excited by the promise our research holds for PKD patients, we have been packaging a variety of PKD drugs into our nanoparticles, testing their ability to act as a courier service for renal drug delivery. We’ve been testing this process on drugs that show therapeutic benefits in animal models but are shadowed by off-target side effects. Because our nanoparticles can carry more than one drug — and even gene therapy — we can help develop and deploy a therapeutic combination that may soon offer patients more benefit than any single drug.
Because the biology of ADPKD is not entirely understood, drug discovery has been slow. As we are seeing with the dramatic success of the COVID-19 vaccines, however, nanomedicine can catalyze research efforts. Nanoparticles offer a promising new way to deliver medicine, making it simultaneously less toxic and more effective.”
Eun Ji Chung is a biomedical engineer.
She shares her story and discusses her KevinMD article, “Using nano ‘couriers’ to deliver PKD drugs to just the right address.”
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Hosted by Kevin Pho, MD, The Podcast by KevinMD shares the stories of the many who intersect with our health care system but are rarely heard from.
Transcript
Kevin Pho: Hi, and welcome to the show, where we share the stories of the many who intersect with our health care system but are rarely heard from. My name is Kevin Pho, founder and editor of KevinMD. Today on the show, we have Eun Ji Chung. She is a biomedical engineer, and she wrote the KevinMD article “Using nano ‘couriers’ to deliver PKD drugs to just the right address.” Eun Ji, welcome to the show.
Eun Ji Chung: Thank you so much for having me. I’m excited to be here.
Kevin Pho: So we’ll get into your article a little bit, but first off, can you share your story and journey to where you are today?
Eun Ji Chung: Yes. So currently I’m an assistant professor in biomedical engineering, and also chemical engineering, surgery, and medicine, at the University of Southern California, so in Los Angeles. I teach nanomedicine and drug delivery, but my lab develops nanobiomaterial-based strategies to deliver drugs for diagnostic applications, primarily focusing on diseases including cardiovascular disease and cancer, and today’s big passion of ours is kidney diseases.
So just a little history about me personally: I was born in Seoul, Korea, and I came to the Midwest when I was about five. I grew up there, lived in California for a bit, and then I actually finished high school at an international school in Korea. Then I came back to the States for college and grad school. In college, I majored in molecular biology, and I was doing research regarding DNA and RNA synthesis, studying them in these unicellular model systems. I think that experience was really exciting, but it really showed me that I wanted to get closer to making a difference for potentially a patient, and to developing some technologies.
So I decided to go into biomedical engineering for my doctoral studies in Chicago, and there I developed these biodegradable, biomimetic, regenerative implants for orthopedic applications, including potentially synthetic ACL replacements. Really, the idea there is: Can we design materials so that they can inform tissue regeneration, and at the end, these materials will go away and degrade, but then newly formed tissue will replace them?
Then from grad school, I wanted to go a little bit more to the molecular scale and the nanoscale. So for my postdoctoral fellowship, I stayed in Chicago, and I developed these nanoparticles that can traffic to biomarkers of plaque. Now, this is in cardiovascular disease and atherosclerosis, trying to understand if we can figure out, on a molecular level, if plaques are likely to rupture. I think this concept of targeting, going to that molecular site and really trying to understand it, and then designing around that, is how it’s woven into my research continually today.
The funny thing is, science is amazing, and it’s so great in this way: You’re studying something for cardiovascular disease, and I was trying to understand how the nanoparticles distribute in animal models, and I found that when we designed the nanoparticles in a specific way, they actually go to the kidneys very efficiently. I thought this was just an amazing insight and an amazing thing that our nanoparticles do, just because nanoparticles don’t typically go to the kidneys. That’s when the idea struck: Why don’t we design these particles so they can deliver drugs for a specific kidney disease? I started getting educated about polycystic kidney disease when I became a professor at USC and started collaborating with Dr. Ken Hallows, who’s the chief of nephrology at USC.
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Kevin Pho: What are the most common applications that nanoparticles are used for today in medicine?
Eun Ji Chung: Nanomedicine is not a totally new concept. The classic example is doxorubicin in liposomal nanoparticles, called Doxil, and those have been FDA-approved since the ’90s. Then of course, more recently, although it’s only for emergency use authorization, our COVID vaccines, the Moderna and the BioNTech Pfizer vaccines, are these lipid nanoparticles that have the mRNA cargo, and they’re injected into our bodies to develop an antibody response against SARS-CoV-2.
It’s been amazing to see the word “nanoparticle” or “mRNA” being just part of common daily conversation. It’s been a crazy, devastating year, but if there was a small silver lining, it’s that there’s been this new light, and there’s been a shedding of light on what nanomedicine technologies can do and their potential.
Kevin Pho: All right, so I’m interested in hearing your applications of this, and you wrote about this in the KevinMD article “Using nano ‘couriers’ to deliver PKD drugs to just the right address.” Now, for those who didn’t get a chance to read your article, can you just walk my audience through it and share the story of why you decided to write it?
Eun Ji Chung: So I wanted to first explain polycystic kidney disease, because that’s not necessarily something that everyone knows. Although autosomal dominant polycystic kidney disease, or ADPKD, is the most commonly inherited, prevalent kidney disease, as well as just one of the more common genetic diseases worldwide, there’s just not much known about it for the everyday person.
This is a disease where you have a mutation, and in some subset of your kidney, the cells will overproliferate, and then they’ll form these fluid-filled cysts, to the point where your kidneys enlarge almost to the size of a football. Usually, a kidney is the size of your fist, so you can see how enlarged they are. Then it’ll lead to kidney function decline and then the need for dialysis and transplantation.
So when I saw that observation, as I was mentioning earlier, I knew that kidney disease was something where we were going to go. When I came to USC, I was very enthusiastically, profusely emailing the nephrology department. Dr. Ken Hallows was very receptive, and this is where the scientists and the clinicians really work so well together: He was informing me about what’s the latest in PKD. At the time, there were zero FDA-approved drugs; this was in 2016. In 2018, there became one FDA-approved drug, and just things in the pipeline. So this field is constantly changing.
As I was scouring through the literature, there were no nanomedicine efforts for PKD, and there are very few efforts for kidney disease in general. I thought that was just the strangest thing, because nanomedicine for cancer is not a new thing, as I was mentioning earlier. And especially with the COVID vaccines, I thought, “You know what? This might be a good time, when people are now familiar with nanoparticles and what they can do.”
How the article started was that I got connected with Bill Brazell, who is one of the board members at the PKD Foundation, and in his professional life, he’s in communication. So we got to talk, and he just thought, “Wow, there’s just so much potential,” and he started to really advocate for this. So I got connected with you, and I wrote the article, and I thought there could be a lot more light shed on PKD, as well as on the potential of nanomedicine for PKD.
The other thing that I wanted to mention today is that, just by coincidence, the PKD Connect conference is happening in real time right now. This is an amazing conference, because out of all the conferences that I know, this is the only one where the patients and the researchers are in the same room together. So they’re coming into my poster session, I’m learning about their challenges, and it’s very informative. I think what I’ve heard from a lot of patients is that the regular nephrologist doesn’t really know much about ADPKD either, and so they can give information about potentially tolvaptan, which is that one FDA-approved drug, but not necessarily about all the different advances. Again, this is a constantly changing field. So I think it would be amazing to have researchers, biomedical engineers, patients, clinicians, and nephrologists all get together and try to really move the needle.
Kevin Pho: Give us a sense of how far down the pipeline we are. How long will it take before we get any potential clinical trials of the approach you suggest?
Eun Ji Chung: I’m hopeful. I started to get into this field a little less than five years ago. At that time, I would have thought, “I am not sure. Let’s see where this goes.” But now that we’ve come this far, and we know a little bit about what our technology can do for PKD, I feel like within the next five to 10 years, which is my personal goal, I think we can potentially find maybe a subset of PKD patients that this might be appropriate for. So that is what I’m projecting, although that’s based on many things, so don’t hold me to it. But that is ultimately what I think is possible.
Kevin Pho: And when working with nanoparticles, and you mentioned that the Pfizer-BioNTech mRNA vaccine is an example of that, what would you say are the biggest challenges of using this technology?
Eun Ji Chung: So I can’t compare it with the COVID vaccine, just because those are getting injected basically into our skin, into our muscles, whereas other types of nanoparticles, potentially for cancer, are IV-injected, because for cancer patients, intravenous infusion or injection is the way that the drug is systemically delivered.
The challenge for chronic disease patients is that this is, especially for patients with hereditary disease, and I must say that this patient population is very well-informed. They know what is going on, they are at the conference, and they want to understand exactly what is happening. So they are a very informed patient population, which is amazing. They know, potentially from an earlier age, that they have a genetic disease that was passed on, just from family history.
For us, though, there are definitely different challenges. For instance, for us, nanomedicine has to be delivered in a manner where it doesn’t affect the patients’ lives. It has to be within the daily routine. You can’t expect a patient to go to the hospital and get an IV infusion every day or something; that doesn’t really help their quality of life.
With oral delivery, which is another part of the lab that is working on PKD, there are challenges to this too. When you take Tylenol or any other drug, it has to go through your stomach into your intestines. It will surpass that barrier, but only a small percentage will go into your blood. It’ll circulate, and then only a small subset of that will go to the right place, and then you won’t feel a headache, etc. So for us, it’s about being able to cross those oral delivery barriers: Don’t get degraded in the stomach, have a bigger depot in the blood, and then our nanoparticles can do their thing, go to the kidneys, and deliver that drug. So it’s about designing the material to efficiently go through these different physiological processes.
Kevin Pho: We’re talking to Eun Ji Chung. She is a biomedical engineer, and she wrote the KevinMD article “Using nano ‘couriers’ to deliver PKD drugs to just the right address.” Eun Ji, in the next few years, as a practicing clinician myself, what could I expect to be the next breakthrough when it comes to nanoparticles in my daily clinical life?
Eun Ji Chung: I think right now, what I’m seeing from the research side, even from biotech companies, because they also have grant proposals, is that they’re very focused on nanomedicine, especially nanoparticle platforms, because they’re understanding now, especially with the COVID vaccines, that there was a lot of underlying research that was done. It might seem like the development was super fast, in a very shortened time, but it wasn’t. It was decades of research that informed the COVID vaccines to be developed correctly, and now it was able to be scaled and it was able to take off. I think that’s going to be applied in many different disease settings.
So I wouldn’t be surprised if you start to see these types of drugs encapsulated into nanoparticles, because they can more efficiently get to the right place without getting diluted in other tissues that are going to cause side effects. I think that type of theme and technology is going to pop up more and more from this point on.
Kevin Pho: And my final question: What’s your take-home message that you want to leave with the KevinMD audience?
Eun Ji Chung: I would like to leave with the message that there is huge potential for nanomedicine. And for the PKD community, I just advocate for nephrologists to continue to learn about ADPKD, the research behind ADPKD, and the challenges that patients face, because this is a generational challenge as well. So for them to just get more involved in the advances, because in this particular field, it’s just changing year by year.
Kevin Pho: Well, thank you so much for sharing your time and insight, and thanks again for being on the show.
Eun Ji Chung: Great. Thank you for having me.
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