Following is the full text of cancer researcher Joy Wolfram’s talk titled “The Promise of Nanomedicine” at TEDxJacksonville conference.
TRANSCRIPT:
It was a Sunday afternoon back in April of this year. My phone was ringing, I picked it up.
The voice said, “It’s Rebecca. I’m just calling to invite you to my funeral.”
I said, “Rebecca, what are you talking about?”
She said, “Joy, as my friend, you have to let me go. It’s my time.”
The next day, she was dead.
Rebecca was 31 years old when she died. She had an eight-year struggle with breast cancer. It came back three times. I failed her.
The scientific community failed her. And the medical community failed her. And she’s not the only one. Every five seconds, someone dies of cancer.
Today, we medical researchers are committed to having Rebecca and people like her be one of the last patients that we fail.
The U.S. government alone has spent over 100 billion on cancer research since the 1970s, with limited progress in regards to patient survival, especially for certain types of very aggressive cancers. So we need a change because, clearly, what we’ve been doing so far has not been working.
And what we do in medicine is to send out firefighters, because cancer is like a big fire. And these firefighters are the cancer drugs.
But we’re sending them out without a fire truck — so without transportation, without ladders and without emergency equipment. And over 99% of these firefighters never make it to the fire. Over 99% of cancer drugs never make it to the tumor because they lack transportation and tools to take them to the location they’re aiming for.
Turns out, it really is all about location, location, location.
So we need a fire truck to get to the right location.
And I’m here to tell you that nanoparticles are the fire trucks. We can load cancer drugs inside nanoparticles, and nanoparticles can function as the carrier and necessary equipment to bring the cancer drugs to the heart of the tumor.
SO WHAT ARE NANOPARTICLES, AND WHAT DOES IT REALLY MEAN TO BE NANO-SIZED?
Well, there are many different types of nanoparticles made out of various materials, such as metal-based nanoparticles or fat-based nanoparticles.
But to really illustrate what it means to be nano-sized, I took one of my hair strands and placed it under the microscope. Now, I have very thin hair, so my hair is approximately 40,000 nanometers in diameter. So this means, if we take 400 of our nanoparticles and we stack them on top of each other, we get the thickness of a single hair strand.
I lead a nanoparticle laboratory to fight cancer and other diseases at Mayo Clinic here in Jacksonville. And at Mayo Clinic, we really have the tools to make a difference for patients, thanks to the generous donations and grants to fund our research.
AND SO, HOW DO THESE NANOPARTICLES MANAGE TO TRANSPORT CANCER DRUGS TO THE TUMOR?
Well, they have an extensive toolbox. Cancer drugs without nanoparticles are quickly washed out of the body through the kidneys because they’re so small. So it’s like water going through a sieve. And so they don’t really have time to reach the tumor.
Here we see an illustration of this. We have the firefighters, the cancer drugs. They’re circulating in the blood, but they’re quickly washed out of the body and they don’t really end up inside the tumor.
But if we put these cancer drugs inside nanoparticles, they will not get washed out by the body because the nanoparticles are too big. And they will continue to circulate in the blood, giving them more time to find the tumor.
And here we see the cancer drug, the firefighters, inside the fire truck, the nanoparticles. They’re circulating in the blood, they don’t get washed out and they actually end up reaching the tumor.
AND SO WHAT OTHER TOOLS DO NANOPARTICLES HAVE?
Well, they can protect cancer drugs from getting destroyed inside the body. There are certain very important but sensitive drugs that are easily degraded by enzymes in the blood. So unless they have this nanoparticle protection, they will not be able to function.
Another nanoparticle tool are these surface extensions that are like tiny hands with fingers that grab on to the tumor and fit exactly onto it, so that when the nanoparticles are circulating, they can attach onto the cancer cells, buying the cancer drugs more time to do their job. And these are just some of the many tools that nanoparticles can have.
And today, we have more than 10 clinically approved nanoparticles for cancer that are given to patients all over the world. Yet, we have patients, like Rebecca, who die.
SO WHAT ARE THE MAJOR CHALLENGES AND LIMITATIONS WITH CURRENTLY APPROVED NANOPARTICLES?
Well, a major challenge is the liver, because the liver is the body’s filtration system, and the liver recognizes and destroys foreign objects, such as viruses, bacteria and also nanoparticles.
And the immune cells in the liver eat the nanoparticles, preventing them from reaching the tumor. And here we see an illustration where the kidney is no longer a problem, but these fire trucks, the nanoparticles, get stuck in the liver and, actually, less of them end up reaching the tumor.
So a future strategy to improve nanoparticles is to temporarily disarm the immune cells in the liver.
SO HOW DO WE DISARM THESE CELLS?
Well, we looked at drugs that were already clinically approved for other indications to see if any of them could stop the immune cells from eating the nanoparticles. And unexpectedly, in one of our preclinical studies, we found that a 70-year-old malaria drug was able to stop the immune cells from internalizing the nanoparticles so that they could escape the liver and continue their journey to their goal, the tumor.
And here we see the illustration of blocking the liver. The nanoparticles don’t go there, and they instead end up in the tumor. So, sometimes, unexpected connections are made in science that lead to new solutions.
Another strategy for preventing nanoparticles from getting stuck in the liver is to use the body’s own nanoparticles. Yes — surprise, surprise. You, and you and you, and all of us have a lot of nanoparticles circulating in our bodies. And because they’re part of our bodies, the liver is less likely to label them as foreign.
And these biological nanoparticles can be found in the saliva, in the blood, in the urine, in pancreatic juice. And we can collect them from the body and use them as fire trucks for cancer drugs. And in this case, the immune cells in the liver are less likely to eat the biological nanoparticles. So we’re using a Trojan-horse-based concept to fool the liver.
And here we see the biological nanoparticles circulating in the blood. They don’t get recognized by the liver, and they end up in the tumor. And in the future, we want to exploit nature’s own nanoparticles for cancer drug delivery, to reduce side effects and save lives by preventing the cancer drugs from being in the wrong location.
However, a major problem has been: How do we isolate these biological nanoparticles in large quantities without damaging them? My lab has developed an efficient method for doing this. We can process large quantities of liquids from the body to produce a highly concentrated, high-quality formulation of biological nanoparticles. And these nanoparticles are not yet in clinical use, because it takes an average of 12 years to get something from the lab to your medicine cabinet.
And this is the type of challenge that requires teamwork from scientists and physicians, who dedicate their lives to this battle. And we keep going, thanks to inspiration from patients. And I believe that if we keep working on these nanomedicines, we will be able to reduce harm to healthy organs, improve quality of life and save future patients.
I like to imagine that if these treatments had been available for Rebecca, that call from her could have been an invitation not to her funeral, but her wedding.
