How nanoparticles could change the way we treat cancer | Joy Wolfram

74,527 views ・ 2019-11-06

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