A new superweapon in the fight against cancer | Paula Hammond

Summary

This script discusses the innovative approach of using molecular engineering to combat aggressive forms of cancer. It introduces siRNA, a molecule that can silence cancer cell survival genes, and describes the development of a nanoparticle that delivers siRNA and chemotherapy drugs directly to cancer cells. The nanoparticle's design allows it to evade the body's immune system, reach the tumor, and effectively target and destroy cancer cells. The strategy has shown promise in animal models, offering a personalized and potent method to combat drug-resistant cancers like triple-negative breast cancer and ovarian cancer.

Takeaways

• 🔬 **Cancer's Complexity**: Cancer is a complex disease with some forms being highly invasive, drug-resistant, and recurring despite treatment.
• 🛡️ **Supervillain Analogy**: Aggressive cancers are likened to supervillains with 'superpowers' derived from genetic mutations, making them adept at evading treatments.
• 🧬 **Gene Mutations**: Genetic mutations within tumor cells can enable cancer to survive by employing various tricks, such as expelling drugs before they can act.
• 💊 **siRNA's Role**: siRNA molecules can target and block specific genes within cells, offering a potential method to combat cancer's genetic defenses.
• 🚫 **siRNA's Challenge**: siRNA is effective inside cells but vulnerable to degradation by enzymes in the bloodstream, necessitating protective measures for in vivo use.
• 🛡️ **Nanoparticle Design**: A nanoparticle with a chemotherapy drug core and an siRNA shell is proposed to protect the siRNA and deliver it to cancer cells.
• 🔄 **Charge Shielding**: A positively charged polymer layer shields the negatively charged siRNA, preventing degradation and ensuring the nanoparticle's stability in the bloodstream.
• 🎯 **Targeting Tumor Cells**: An additional layer of naturally occurring, negatively charged polysaccharides disguises the nanoparticle, allowing it to evade the immune system and target tumor cells.
• 🐁 **Animal Testing**: The strategy's effectiveness was demonstrated in animal models with triple-negative breast cancer, showing tumor regression with the nanoparticle treatment.
• 🌟 **Personalization Potential**: The treatment approach can be personalized by varying the siRNA and drug core components to target different genetic mutations and tumor types.

Q & A

What is the main challenge in treating aggressive forms of cancer?

Aggressive forms of cancer are challenging to treat because they can be highly invasive, drug-resistant, and defy medical treatments, including chemotherapy.

How do some cancer cells survive chemotherapy treatments?

Some cancer cells survive chemotherapy treatments due to genetic mutations that allow them to develop new modes of survival, such as pumping out the drugs before they can take effect.

What is the role of siRNA in cancer treatment as described in the script?

siRNA (small interfering RNA) is used to block specific genes within cancer cells, effectively turning off their 'survival genes' and making them more susceptible to chemotherapy.

Why is siRNA not effective on its own when introduced into the body?

siRNA degrades within seconds when exposed to enzymes in the bloodstream or tissues, so it needs to be protected during its journey to the cancer cells.

How is the nanoparticle designed to protect the siRNA and deliver it to cancer cells?

The nanoparticle is designed with a core containing the chemotherapy drug, surrounded by a thin layer of siRNA, which is then protected by a positively charged polymer layer. An outer layer of negatively charged, highly hydrated polysaccharides provides an invisibility cloaking effect and targeting molecules for the tumor cells.

What is the strategy for deploying the nanoparticle in cancer treatment?

The strategy involves dosing the cancer cells with siRNA to silence survival genes, followed by the release of the chemotherapy drug from the nanoparticle core to destroy the tumor cell.

How does the outer layer of the nanoparticle help in targeting cancer cells?

The outer layer of the nanoparticle contains molecules that bind specifically to tumor cells, allowing the nanoparticle to be taken up by the cancer cell once it binds.

What was the result of testing the nanoparticle treatment on animals with triple-negative breast cancer?

In animal tests, the combination of siRNA and chemotherapy within the nanoparticle not only stopped tumor growth but also led to tumor regression in some cases.

How can this treatment approach be personalized for different patients?

The treatment can be personalized by adding different layers of siRNA to address various mutations and tumor defense mechanisms, and by using different drugs in the nanoparticle core.

Why is ovarian cancer considered a 'supervillain' in the context of the script?

Ovarian cancer is considered a 'supervillain' because it is very aggressive, often discovered at late stages, and has a high recurrence rate, especially in drug-resistant forms.

What is the significance of the story shared by the mother and daughter, Mimi and Paige, in the script?

Mimi and Paige's story illustrates the emotional impact of cancer and the importance of hope and support. It also emphasizes the potential of new treatments to change lives and the power of engineering at the molecular level to address health challenges.

Outlines

00:00

🧬 Combating Cancer with Molecular Engineering

The paragraph discusses the challenges of treating aggressive and drug-resistant forms of cancer, which can evade conventional treatments. It introduces the concept of using molecular engineering to develop innovative strategies against cancer. The speaker likens these resilient cancers to supervillains with genetic mutations that grant them unique survival abilities. One such ability is the capacity of cancer cells to expel chemotherapy drugs before they can take effect. To counter this, the paragraph introduces the use of siRNA, a molecule that can silence specific genes within cancer cells. However, siRNA is vulnerable to degradation by enzymes in the bloodstream, necessitating a protective delivery mechanism. The strategy proposed involves using siRNA to silence cancer cell survival genes, followed by the application of chemotherapy drugs. The paragraph sets the stage for a detailed explanation of the engineering of a nanoparticle that can carry out this strategy.

05:01

🛡️ Designing a Stealthy Nanoparticle for Cancer Treatment

This paragraph delves into the design of a nanoparticle that can deliver siRNA and chemotherapy drugs directly to cancer cells. The nanoparticle is described as needing to be extremely small, about one one-hundredth the size of a human hair, to navigate the bloodstream and penetrate tumor tissue. The core of the nanoparticle contains the chemotherapy drug, with a thin layer of siRNA wrapped around it. To protect the siRNA from degradation, a positively charged polymer is used, which adheres to the negatively charged siRNA through electrostatic attraction. The paragraph also addresses the challenge of the body's immune system, which recognizes and eliminates foreign objects. To bypass this, an additional layer of negatively charged, naturally occurring polysaccharides is added to the nanoparticle, providing a 'cloak of invisibility' and specific molecules that bind to tumor cells, ensuring the nanoparticle is taken up by the cancer cells. The effectiveness of this approach is demonstrated through animal testing with a highly aggressive form of triple-negative breast cancer, showing that the combination of siRNA and chemotherapy drugs can lead to tumor regression.

10:02

🌟 Personalized Medicine and the Future of Cancer Treatment

The final paragraph emphasizes the potential for personalization in cancer treatment using the described nanoparticle technology. It suggests that different layers of siRNA can be added to target various mutations and tumor defense mechanisms, and different drugs can be incorporated into the nanoparticle core. The speaker shares a personal connection to ovarian cancer and discusses the high rate of recurrence and drug resistance associated with it. The paragraph concludes with a meeting between the speaker and an ovarian cancer survivor, Mimi, and her daughter, Paige, highlighting the emotional impact and hope that advancements in molecular engineering bring to those affected by cancer. The speaker reflects on the importance of engineering at the molecular level not just for scientific elegance but for its life-changing potential.

Keywords

💡Cancer

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. In the context of the video, cancer is likened to a supervillain, emphasizing its cunning and resistance to conventional treatments. The video discusses aggressive forms of cancer that are highly invasive and drug-resistant, highlighting the need for innovative approaches to combat them.

💡Drug Resistance

Drug resistance in cancer refers to the ability of cancer cells to survive and grow despite the presence of drugs that should inhibit their growth. The video explains that some cancers can 'spit out' drugs before they can take effect, rendering traditional chemotherapy less effective. This concept is central to the discussion of why new strategies, like the use of siRNA, are necessary.

💡siRNA (Small Interfering RNA)

siRNA is a type of molecule that can specifically silence genes within cells. In the video, siRNA is described as a 'gene blocker' that can be used to turn off genes that allow cancer cells to survive chemotherapy. The innovative use of siRNA is a key part of the strategy to combat cancer, as it can potentially disable the cancer cell's resistance mechanisms.

💡Molecular Engineering

Molecular engineering involves the design and synthesis of molecules for specific functions. The video discusses the use of molecular engineering to create nanoparticles that can deliver siRNA and chemotherapy drugs directly to cancer cells. This approach is critical for protecting the siRNA from degradation and ensuring it reaches the tumor site effectively.

💡Nanoparticles

Nanoparticles are tiny particles measured in nanometers. In the video, nanoparticles are engineered to carry chemotherapy drugs and siRNA to cancer cells. They are designed to be small enough to penetrate tumor tissue and enter cancer cells, making them a 'superweapon' in the fight against cancer.

💡Gene Mutation

A gene mutation is a change in the DNA sequence that can lead to the production of abnormal proteins or the alteration of gene expression. The video describes how gene mutations can give cancer cells 'superpowers,' such as the ability to expel drugs. Understanding and targeting these mutations is a key aspect of the proposed cancer treatment strategy.

💡Chemotherapy

Chemotherapy is a type of cancer treatment that uses drugs to kill rapidly dividing cells, including cancer cells. The video discusses how certain aggressive forms of cancer can become resistant to chemotherapy, necessitating the development of new treatment methods like the combination of siRNA and chemo drugs within nanoparticles.

💡Triple-Negative Breast Cancer

Triple-negative breast cancer is a subtype of breast cancer that does not express estrogen receptors, progesterone receptors, or HER2/neu proteins, making it more difficult to treat with standard hormone therapies or HER2-targeted drugs. The video uses this type of cancer as an example of a highly aggressive form that can be targeted with the new nanoparticle approach.

💡Personalized Medicine

Personalized medicine is an approach to healthcare that tailors medical treatments to individual patients based on their genetic makeup. In the video, the concept is applied to cancer treatment, where different layers of siRNA can be added to address various mutations and tumor defense mechanisms, allowing for a more targeted and effective treatment plan.

💡Ovarian Cancer

Ovarian cancer is a type of cancer that begins in the ovaries and is often diagnosed at an advanced stage due to its nonspecific early symptoms. The video highlights the aggressive nature of ovarian cancer and its tendency to recur in drug-resistant forms, underscoring the importance of developing new treatment strategies like the nanoparticle approach.

Highlights

Cancer's resistance to treatment is likened to a supervillain's resistance to traditional attacks.

Molecular engineering at the smallest scales offers new ways to combat aggressive cancer forms.

Some cancers are described as 'supervillains' due to their genetic mutations and adaptability.

One mechanism of cancer resistance involves cells ejecting drugs before they can take effect.

siRNA molecules can be used to block specific genes within cells, offering a new approach to cancer treatment.

Challenges in using siRNA include its degradation by enzymes in the bloodstream or tissues.

A strategy is proposed to first use siRNA to silence cancer cell survival genes, followed by chemotherapy.

Nanoparticles are engineered to carry chemotherapy drugs and siRNA, designed to evade the body's immune system.

The nanoparticle core contains the drug, wrapped in siRNA and protected by a positively charged polymer.

An additional layer of negatively charged polysaccharides provides 'invisibility' to the nanoparticle, allowing it to reach the tumor.

The outer layer of the nanoparticle also contains molecules that bind specifically to tumor cells, ensuring targeted delivery.

The siRNA is deployed first to disable the cancer cell's genetic defenses, followed by the release of the chemotherapy drug.

Animal testing with triple-negative breast cancer showed that the combination therapy stopped tumor growth and led to regression.

The approach can be personalized by adding different siRNA layers to address various mutations and drug resistances.

The strategy's potential is highlighted by its application in ovarian cancer, which often recurs in drug-resistant forms.

Personal stories, such as that of an ovarian cancer survivor and her daughter, underscore the human impact of this research.

The potential of molecular engineering to address significant health problems is emphasized, inspiring future generations.

Transcripts

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)