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  • 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 are 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 aggressive forms of cancer

  • as kind of supervillains in a comic book.

  • They're clever, they're adaptable,

  • and they're very good at staying alive.

  • And, like most supervillains these days,

  • their superpowers 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 supervillain, cancer.

  • All due to mutant genes.

  • So, we have a supervillain with incredible superpowers.

  • 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 then we'll whop it with a chemo drug.

  • But how do we carry that out?

  • Using molecular engineering,

  • we can actually design a superweapon

  • that can travel through the bloodstream.

  • It has to be tiny enough to get through the bloodstream,

  • 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 one-hundredth 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, protective layer of positively 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 bloodstream.

  • 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 superweapon?

  • I mean, every good weapon needs to be targeted,

  • we have to target this superweapon to the supervillain cells

  • that reside in the tumor.

  • But our bodies have a natural immune-defense system:

  • cells that reside in the bloodstream

  • and pick out things that don't belong,

  • so that it can destroy or eliminate them.

  • And guess what? 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 polysaccharides that resides in our body.

  • It creates a cloud of water molecules around the nanoparticle

  • that gives us an invisibility cloaking effect.

  • 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 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 aggressive form of triple-negative breast cancer.

  • This triple-negative breast cancer exhibits the gene

  • that spits out cancer drug as soon as it is 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 superweapon.

  • A nanolayer 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 decreased in size

  • and were eliminated 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 aggressive cancer,

  • in part because it's discovered at very late stages,

  • when it's 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 supervillains out there.

  • And we're now directing our superweapon

  • toward 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 possibilities

  • in addressing some of the big health problems in the world --

  • including ovarian cancer, neurological disorders, infectious disease --

  • just as chemical engineering has found a way to open doors for me,

  • and has provided a way of engineering

  • on the tiniest scale, that of molecules,

  • to heal on the human scale.

  • Thank you.

  • (Applause)

Cancer affects all of us --

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B1 US TED cancer tumor gene drug cancer cell

【TED】Paula Hammond: A new superweapon in the fight against cancer (A new superweapon in the fight against cancer | Paula Hammond)

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    江啟和 posted on 2016/07/18
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