Cancer affects all of us,
especially the ones that come back over and over again.
The highly invasive and drug-resistant ones,
the ones that defy medical treatment,
even when we throw our best drugs at them.
Engineering at the molecular level,
working at the smallest of scales,
can provide exciting new ways
to fight the most aggressive forms of cancer.
Cancer is a very clever disease.
There are some forms of cancer,
which, fortunately, we've learned how to address relatively well
with known and established drugs and surgery.
But, there's some forms of cancer that don't respond
to these approaches
and the tumor survives or comes back,
even after an onslaught of drugs.
We can think of these very aggresive forms of cancer
as kind of super villains in a comic book.
They're clever, they're adaptable,
and they're very good at staying alive.
And, like most super villains these days,
their super powers come from a genetic mutation.
The genes that are modified inside these tumor cells
can enable and encode for new and unimagined modes of survival,
allowing the cancer cell to live through
even our best chemotherapy treatments.
One example is a trick in which a gene allows a cell,
even as the drug approaches the cell,
to push the drug out before the drug can have any effect.
Imagine the cell effectively spits out the drug.
This is just one example of the many genetic tricks
in the bag of our super villain, cancer.
All due to mutant genes.
So, we have a super villain with incredible super powers
and we need a new and powerful mode of attack.
Actually, we can turn off a gene,
the key is a set of molecules known as siRNA.
siRNA are short sequences of genetic code
that guide a cell to block a certain gene.
Each siRNA molecule can turn off a specific gene
inside the cell.
For many years since its discovery,
scientists have been very excited
about how we can apply these gene blockers in medicine.
But, there is a problem.
siRNA works well inside the cell.
But if it gets exposed to the enzymes that reside
in our bloodstream or our tissues,
it degrades within seconds.
It has to be packaged, protected through its journey through the body
on its way to the final target inside the cancer cell.
So, here's our strategy:
first, we'll dose the cancer cell with siRNA, the gene blocker,
and silence those survival genes,
and they'll we'll whap it with a chemo drug.
But how do we carry that out?
Using molecular engineering,
we can actually design a super weapon
that can travel through the blood stream.
It has to be tiny enough that it can get through the blood stream,
it's got to be small enough to penetrate the tumor tissue,
and it's got to be tiny enough to be taken up
inside the cancer cell.
To do this job well, it has to be about one 100th the size
of a human hair.
Let's take a closer look at how we can build this nanoparticle.
First, let's start with the nanoparticle core.
It's a tiny capsule that contains the chemotherapy drug.
This is the poison that will actually end the tumor cell's life.
Around this core, we'll wrap a very thin,
nanometers-thin blanket of siRNA.
This is our gene blocker.
Because siRNA is strongly negatively charged,
we can protect it with a nice protect layer
of postively charged polymer.
The two oppositely charged molecules
stick together through charge attraction
and that provides us with a protective layer
that prevents the siRNA from degrading in the blood stream.
We're almost done.
(Laughter)
But there is one more big obstacle we have to think about.
In fact, it may be the biggest obstacle of all.
How do we deploy this super weapon?
I mean, every good weapon needs to be targeted,
we have to target this super weapon to the super villain cells
that reside in the tumor.
But, our bodies have a natural immune defense system.
Cells that reside in the blood stream
and pick out things that don't belong
so that it can destroy or elinate them.
And guess that, our nanoparticle is considered a foreign object.
We have to sneak our nanoparticle
past the tumor defense system,
we have to get it past this mechanism of getting rid of the foreign object
by disguising it.
So we add one more negatively charged layer
around this nanoparticle,
which serves two purposes.
First, this outer layer is one of the naturally charged,
highly hydrated polysaccarides that resides in our bodies.
It creates a cloud of water molecules around the nanoparticle
that gives us an invisibility cloaking affect.
This invisibility cloak allows the nanoparticle
to travel through the bloodstream long and far enough
to reach the tumor without getting eliminated by the body.
Second, this layer contains molecules which bind specifically
to our tumor's cell.
Once bound, the cancer cell takes up the nanoparticle
and now we have our nanoparticle inside the cancer cell
and ready to deploy.
Alright, I feel the same way, let's go.
(Applause)
The siRNA is deployed first.
It acts for hours,
giving enough time to silence and block those survival genes.
We have now disabled those genetic superpowers.
What remains is a cancer cell with no special defenses.
Then, the chemotherapy drug comes out of the core
and destroys the tumor cell cleanly and efficiently.
With sufficient gene blockers,
we can address many different kinds of mutations.
Allowing the chance to sweep out tumors, without leaving behind any bad guys.
So, how does our strategy work?
We've tested these nanostructure particles in animals
using a highly aggresive form of triple negative breast cancer.
This triple negative breast cancer exhibits the gene
that spits out cancer drugs as soon as its delivered.
Usually, doxorubicin, let's call it dox,
is the cancer drug that is the first line of treatment
for breast cancer.
So, we first treated our animals with a dox core, dox only.
The tumor slowed their rate of growth,
but they still grew rapidly,
doubling in size over a period of two weeks.
Then, we tried our combination super weapon.
And now layer a particle with siRNA against the chemo pump,
plus, we have the dox in the core.
And look, we found that not only did the tumors stop growing,
they actually decerased in size
and were elimintaed in some cases.
The tumors were actually regressing.
(Applause)
What's great about this approach is that it can be personalized,
we can add many different layers of siRNA
to address different mutations and tumor defense mechanisms
and we can put different drugs into the nanoparticle core.
As doctors learn how to test patients and understand
certain tumor genetic types,
they can help us determine which patients
can benefit from this strategy
and which gene blockers we can use.
Ovarian cancer strikes a special chord with me.
It is a very aggresive cancer,
in part because it's discovred at very late stages
when its highly advanced
and there are a number of genetic mutations.
After the first round of chemotherapy,
this cancer comes back for 75 percent of patients.
And it usually comes back in a drug resistant form.
High-grade ovarian cancer is one of
the biggest super villains out there.
And we're now directlng this super weapon
towards its defeat.
As a researcher,
I usually don't get to work with patients,
but I recently met a mother
who is an ovarian cancer survivor, Mimi and her daughter pAIGE.
I was deeply inspired
by the optimism and strength
that both mother and daughter displayed.
And by their story of courage and support.
At this event, we spoke about the different technologies
directed at cancer.
And Mimi was in tears as she explained how
learning about these efforts
gives her hope for future generations,
including her own daughter.
This really touched me.
It's not just about building really elegant science,
it's about changing people's lives.
It's about understanding the power of engineering
on the scale of molecules.
I know that as students like Paige
move forward in their careers,
they'll open new possibilites
in addressing some of the big health problems in the world.
Including, ovarian cancer, neurological disorders,
and infectious disease.
Just as chemical engineering has found a way
to open doors for me.
Has provided a way of engineering on the tiniest scale
that of molecules
to heal on the human scale.
Thank you
(Applause)