Rehab Cell

Physical Medicine and Rehabilitation

Targeted Therapy for Liver Cancer Assisted by Nanotechnology | Taeghwan Hyeon | TEDxKFAS

Translator: Enid Kim
Reviewer: Emma Gon Today I’m going to talk about
how nanotechnology can fight against a devastating disease called liver cancer. Liver cancer is really nasty stuff. Actually it’s responsible for more
than 12,000 deaths in United States only every year. This is really devastating. Even more so is that once you’re diagnosed
with liver cancer, only 30% – less than 30%
of patients can be eligible for conventional surgical interventions. The rest of 70% is something
like death sentence. Because conventional anti-cancer drugs such as doxorubicin and cisplatin [are] not working for liver cancer. The best FDA approved
therapy for liver cancer – liver cancer is also known as Hepatocellular Carcinoma or HCC – the best therapy approved by FDA, US FDA, is called the Nexavar, commercialized
by Bayer Pharmaceuticals. What it does is it only extends
lifespan for two more months. Basically, using the cutting-edge,
best therapy for the liver cancer, you can live two months longer. It is really bad. It’s terrible. So we need something. That’s why I jump in with my expertise
in nanoparticle and nanotechnology. That’s my expertise. How nanotechnology can jump in to fight against this devastating disease? Basically first, we try to find
the best one. Which is going to work
for the fight against this liver cancer. And then we’re going to combine
that with nanotechnology to make it a lot more efficient, therapeutic-wise and also very importantly, how are we going to relieve side effects? That’s what I’m going to show now. First, there are thousands –
many different kinds – of potential candidates
for the liver cancer. And actually, there’s bunch of them in the anticancer agent available. And also, there’s a lot of natural product potentially used for anticancer agent. We actually screened. We performed drug screening process
[on] over thousand of compounds available. And then the winner is this guy. The winner is Triptolide. Actually interestingly, Triptolide is extracted
from a plant called, in English word is Thunder God Vine, and Chinese word is Leigongteng. And this is actually as the name says, this is Chinese medicine. And actually, more than thousands
of years ago in China this Leigongteng was used
to treat fever and edema. And Triptolide actually
is the active component extracted from Leigongteng. Alright? So we got the material, the compound,
the best one we got. Which is going to fight
against liver cancer. But we have some serious problems. Which is, it’s way too good. The problem is too much toxic. Remember anticancer agent is a toxin. Toxins are not selective. We designed toxins
to fight against cancer, but not only that anticancer
agent kills tumor cells but also it affects normal tissue, and normal cells too. That’s how we see
a lot of serious side effect of the anticancer agent therapy. Like, often times vomiting, nausea and having trouble to eat food and hair loss. That’s typical side effect. Right? This is really a serious problem. This is going to be even more serious like Triptolide because it itself
has a huge toxicity already. So how to use this best selected, the best therapeutic agent
for liver cancer but relieve side effects? In order to do that, first we have to understand fundamentals of cancers. One of the first principles, first characteristic of cancer cells,
tumor cells is that they grow abnormally fast. They grow really fast compared
to normal tissues or normal cells, cancer cells, tumor cells
grow extremely fast. Because it grows really fast, there are several things that can happen. Two major things I’m going
to talk about here are, first, as we exercise very hard, it produces a lot of lactic acids, right? Through something called
the glycolysis process. Actually, I love tennis. Actually, to be honest with you even last night I played tennis.
(Laughter) I usually play in the afternoon but you know, yesterday was so hot, right? Over 35 degrees Celsius, too hot and then I played at night. But don’t worry,
I just played one game, OK? To save some more energy for this talk. When you exercise a lot, you produce a lot of lactic acid. Likewise, rapidly growing cancer cells produce a bunch of lactic acid. Here’s some hint – our normal tissue is neutral like drinking water. pH of 7.4. It’s like drinking water. Neutral. On the other hand, tumor cell is slightly acidic. Not that much. pH value around… may go down to the 5.5,
which is extremely-diluted vinegar. Slightly acidic, but we can utilize that slight acidity. Second thing is, as I mentioned earlier, cancer cells grow really fast and also for the cells to grow
we need blood supply, right? Blood comes through blood vessels,
obviously, right? But near the normal blood vessel has a slowly growing – that blood vessel
is a perfectly well order structures. But like anything done really in haste, blood vessel in tumor is not well done. There’s a bunch of loopholes. There’s bunch of holes there. So two things, because cancer cells grow abnormally fast,
there are two characteristics. One, they are slightly acidic through that the formation
of a bunch of lactic acid. Second thing is blood vessel
has a bunch of holes in it. That’s how nanotechnologies can jump in. We pick up that Triptolide, remember? The champion drug we screened.
We got it. Because it is too toxic, we made that as nanoparticle. We do special stuff here, which is acid-sensitive polymer. In other words, those nanoparticles
compose of acid-sensitive polymer. So in neutral or normal tissues, it keeps that nanoparticle shape. But when it goes to the tumor side,
it’s acidic, right? As I told you. It disintegrates. Like grenade. Remember this is nanogrenade.
This is a good grenade. Not bad one, OK? So like a grenade, a normal tissue,
nothing happens. It just keeps a nanoparticle shape. Second function, I put in here
is missile-guidance. Again, this missile is good missile.
Don’t worry about it, OK? So this missile, as you know,
the guided missile – on the head of the missile
is guidance, right? So guiding to the target, we anchored so called folate ligand. That folate ligand is specifically
bind to liver cancer circuits. You put that as a missile guidance system
on top of the nanoparticle. So in a normal tissue, nothing happens, it keeps the good nanoparticle shape. But when it goes to the tumor, because there’s a whole bunch
of holes in it, it gets in. It more efficiently gets in
because now we have a missile guidance system. Folate ligand on the surface. It more effectively,
slip through the holes in the tumor blood vessel. Once it gets in, now it’s acidic, right? What’s going to happen? Like an explosion of grenade, it explodes, and releasing that Triptolide
in the cancer agent. This is our idea. Let’s first look at the –
is missile guidance actually working? Yes, it’s working. As we can show here that drop in nanoparticle form
selectively accumulates in liver. And what it does…
now its missile’s working, right? And then, as shown here,
we select control. Control is just like diluted salt water. Like in your contact lens
cleansing solution. We call it physiological
saline solution as control. As you can see, cancers grow and grow… 40 days later it’s a huge size
in cancer… tumor size. When you treat with a free Triptolide,
without doing anything, just free Triptolide, it does show some therapeutic effect. As you can see,
cancer tumor size decreases. But the problem is body weight,
which is signature of toxicity, body weight significantly decreases. Significant body weight loss. That means it’s toxic. That’s why you cannot use it as it is. Finally, our nanoparticle
form of Triptolide, with a grenade and missile function. As you can see, tumor size significantly decreases
and body weight actually start increasing. That means there’s not
that much toxicity at all, right? Final slide I will show you. As shown here, here, the model we have used is the so called orthotopic xenograft. Basically, we took a cancer cell, a liver cancer cell
from liver cancer patient and then [implanted it] to mouse and that means this is very close
to real cancer patient model. And as you can see,
three months later control the survival
only less than 30% survival. Our nano formulated Triptolide
as you can see, survival rate increased to 80%. This is the message
I’m going to give you today. Personally, my both families
have died of cancer. I have a vision, not only as professor and scientist, I’m interested in publishing nice papers. But eventually, what I’m doing can benefit in the future, a lot of suffering patients, so that my nanotechnology
does not just belong to me, it can help others,
many other people’s lives. Thank you very much.

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