How nanoparticles could change the way we treat cancer Joy Wolfram
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 US 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 percent of these firefighters
never make it to the fire.
Over 99 percent 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.
(Laughter)
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.
Thank you.
(Applause)