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

譯者: Lilian Chiu 審譯者: SF Huang

It was a Sunday afternoon back in April of this year.

今年四月的一個星期日下午，

My phone was ringing,

我的電話響了，

I picked it up.

我接起來。

The voice said, "It's Rebecca.

對方說：「我是瑞貝卡。

I'm just calling to invite you

我打電話來是想邀請你

to my funeral."

參加我的葬禮。」

I said, "Rebecca, what are you talking about?"

我說：「瑞貝卡，你在說什麼啊？ 」

She said, "Joy, as my friend, you have to let me go.

她說：「喬伊，身為我的朋友，

你得放手讓我走。

It's my time."

我的時候到了。」

The next day, she was dead.

隔天，她過世了。

Rebecca was 31 years old when she died.

瑞貝卡過世時才三十一歲。

She had an eight-year struggle with breast cancer.

她花了八年時間對抗乳癌。

It came back three times.

她經歷了三次復發。

I failed her.

我辜負了她。

The scientific community failed her.

科學界辜負了她。

And the medical community failed her.

醫學界辜負了她。

And she's not the only one.

且她不是唯一被辜負的人。

Every five seconds,

每五秒鐘，

someone dies of cancer.

就有一個人死於癌症。

Today, we medical researchers are committed

現今，我們醫學研究者致力於

to having Rebecca and people like her

讓瑞貝卡及像她這樣的人

be one of the last patients that we fail.

成為我們所辜負的最後一批人。

The US government alone has spent over 100 billion on cancer research

從七〇年代起， 光是美國政府就投入了

超過一千億美金在癌症研究上，

since the 1970s,

with limited progress in regards to patient survival,

但在病人存活率的進展上非常有限，

especially for certain types of very aggressive cancers.

對於某些侵襲性極強的癌症更是如此。

So we need a change because, clearly,

所以我們必須改變，因為很顯然，

what we've been doing so far has not been working.

目前為止我們所做的沒什麼效果。

And what we do in medicine is to send out firefighters,

在醫學上，我們所做的， 就是派出打火弟兄，

because cancer is like a big fire.

因為癌症就像是熊熊大火。

And these firefighters are the cancer drugs.

這些打火弟兄就是抗癌藥物。

But we're sending them out without a fire truck --

但我們派他們出去時， 沒有給他們消防車——

so without transportation, without ladders

沒有交通工具，沒有梯子，

and without emergency equipment.

沒有緊急裝備。

And over 99 percent of these firefighters never make it to the fire.

超過 99% 的打火弟兄

沒有趕到火場。

Over 99 percent of cancer drugs never make it to the tumor

超過 99% 的抗癌藥物 沒有到達腫瘤所在之處，

because they lack transportation and tools

因為它們缺乏運輸方式與工具

to take them to the location they're aiming for.

帶它們到要殲滅的目標那兒去。

Turns out, it really is all about location, location, location.

結果發現，重點都在於 地點，地點，地點。

(Laughter)

（笑聲）

So we need a fire truck to get to the right location.

所以，我們需要消防車 前往對的地點。

And I'm here to tell you that nanoparticles are the fire trucks.

我來這裡是要告訴各位， 奈米粒子就是消防車。

We can load cancer drugs inside nanoparticles,

我們能把抗癌藥物裝載到奈米粒子中，

and nanoparticles can function as the carrier

奈米粒子扮演的角色是運輸工具

and necessary equipment

以及必要的裝備，

to bring the cancer drugs to the heart of the tumor.

能將抗癌藥物帶到腫瘤的核心地帶。

So what are nanoparticles,

所以，奈米粒子是什麼？ 奈米大小又是什麼意思？

and what does it really mean to be nano-sized?

Well, there are many different types of nanoparticles

奈米粒子的種類很多，

made out of various materials,

它們的組成材料也不同，比如，

such as metal-based nanoparticles

有以金屬為基礎的奈米粒子，

or fat-based nanoparticles.

也有以脂肪為基礎的奈米粒子。

But to really illustrate what it means to be nano-sized,

但，為了清楚說明奈米大小是什麼，

I took one of my hair strands

我拿了我的一根頭髮，

and placed it under the microscope.

把它放在顯微鏡下。

Now, I have very thin hair,

我的頭髮算很細，

so my hair is approximately 40,000 nanometers in diameter.

我的頭髮直徑大約是四萬奈米。

So this means, if we take 400 of our nanoparticles

意思就是，把四百個奈米粒子

and we stack them on top of each other,

一個一個堆疊起來，

we get the thickness of a single hair strand.

就會跟我的一根頭髮的厚度一樣。

I lead a nanoparticle laboratory to fight cancer and other diseases

我領導著一間奈米粒子實驗室， 旨在對抗癌症及其他疾病，

at Mayo Clinic here in Jacksonville.

位在傑克遜維爾的梅奧診所。

And at Mayo Clinic,

在梅奧診所，我們真的有些工具

we really have the tools to make a difference for patients,

能夠為病人帶來不同的結果，

thanks to the generous donations and grants to fund our research.

這些都要歸功慷慨贊助 我們研究的外界捐贈和獎助金。

And so, how do these nanoparticles manage to transport cancer drugs

所以，這些奈米粒子 要如何將抗癌藥物

運輸到腫瘤所在之處？

to the tumor?

Well, they have an extensive toolbox.

奈米粒子有個很大的工具箱。

Cancer drugs without nanoparticles are quickly washed out of the body

沒有奈米粒子，抗癌藥物很快就會

經由腎臟排出體外，

through the kidneys

because they're so small.

因為它們太小了。

So it's like water going through a sieve.

所以，那就像是水通過篩網。

And so they don't really have time to reach the tumor.

這些藥物真的 沒有時間到達腫瘤所在之處。

Here we see an illustration of this.

這張圖就是在說明這一點。

We have the firefighters, the cancer drugs.

我們有打火弟兄（抗癌藥物）。

They're circulating in the blood,

它們在血液中循環流動，

but they're quickly washed out of the body

但它們很快就被排出體外，

and they don't really end up inside the tumor.

它們最後不會到達腫瘤內。

But if we put these cancer drugs inside nanoparticles,

但如果我們把這些抗癌藥物 放在奈米粒子中，

they will not get washed out by the body

它們不會被排出體外，

because the nanoparticles are too big.

因為奈米粒子太大了。

And they will continue to circulate in the blood,

它們會持續在血液中循環，

giving them more time to find the tumor.

讓它們有更多的時間找到腫瘤。

And here we see the cancer drug, the firefighters,

在這裡，我們可以看到 抗癌藥物（打火弟兄），

inside the fire truck, the nanoparticles.

它們在消防車（即奈米粒子）中。

They're circulating in the blood,

它們在血液中循環， 它們沒有被排出體外，

they don't get washed out

and they actually end up reaching the tumor.

它們最後真的抵達了腫瘤處。

And so what other tools do nanoparticles have?

所以，奈米粒子 還有什麼其他工具？

Well, they can protect cancer drugs from getting destroyed inside the body.

它們可以保護抗癌藥物 使其在體內時不會被摧毀。

There are certain very important but sensitive drugs

有些非常重要但很敏感的藥物

that are easily degraded by enzymes in the blood.

在血液中很容易被酵素給破壞分解。

So unless they have this nanoparticle protection,

若沒有這種奈米粒子保護，

they will not be able to function.

它們就無法發揮功能。

Another nanoparticle tool are these surface extensions

奈米粒子的另一項工具 就是這些表面延伸物，

that are like tiny hands with fingers that grab on to the tumor

就像小手上的手指頭可以抓住腫瘤，

and fit exactly onto it,

完全緊密貼合住腫瘤，

so that when the nanoparticles are circulating,

所以，當奈米粒子在循環時，

they can attach onto the cancer cells,

它們就能附著在癌細胞上，

buying the cancer drugs more time to do their job.

幫抗癌藥物爭取更多時間 來盡它們的本份。

And these are just some of the many tools that nanoparticles can have.

奈米粒子還有許多工具， 這些只是其中一部分。

And today,

現今，

we have more than 10 clinically approved nanoparticles for cancer

已經有十種以上通過臨床 測試的抗癌用奈米粒子，

that are given to patients all over the world.

已經用在世界各地的病人身上。

Yet, we have patients, like Rebecca, who die.

但，我們有些病人 和瑞貝卡一樣過世了。

So what are the major challenges and limitations

所以，這些目前已核准的奈米粒子

with currently approved nanoparticles?

主要遇到什麼困難及限制？

Well, a major challenge is the liver,

其中一個主要困難是肝臟，

because the liver is the body's filtration system,

因為肝臟是身體的過濾系統，

and the liver recognizes and destroys foreign objects,

肝臟會辨視出外來物並將之摧毀，

such as viruses, bacteria and also nanoparticles.

比如病毒、細菌以及奈米粒子。

And the immune cells in the liver eat the nanoparticles,

而肝臟中的免疫細胞會吃掉奈米粒子，

preventing them from reaching the tumor.

讓它們無法抵達腫瘤所在之處。

And here we see an illustration where the kidney is no longer a problem,

從這張圖上可以看到 腎臟已經不是問題，

but these fire trucks, the nanoparticles,

但這些消防車（奈米粒子）

get stuck in the liver

會困在肝臟中，

and, actually, less of them end up reaching the tumor.

所以它們當中只有少數能到達腫瘤處。

So a future strategy to improve nanoparticles

所以，未來在改善奈米粒子的策略上，

is to temporarily disarm the immune cells in the liver.

就是暫時解除肝臟免疫細胞的武裝。

So how do we disarm these cells?

我們要如何解除這些細胞的武裝？

Well, we looked at drugs that were already clinically approved

我們去研究了已通過臨床測試

for other indications

用於其他適應症的藥品，

to see if any of them could stop the immune cells

看是否能從裡面找出能阻止免疫細胞

from eating the nanoparticles.

吞噬掉奈米粒子的品項。

And unexpectedly, in one of our preclinical studies,

出乎意料，在我們的 一項臨床前研究中，

we found that a 70-year-old malaria drug

我們發現有七十年歷史的瘧疾藥物

was able to stop the immune cells from internalizing the nanoparticles

能夠阻止免疫細胞將奈米粒子內化，

so that they could escape the liver

如此奈米粒子便能逃過肝臟，

and continue their journey to their goal, the tumor.

繼續邁向目的地：腫瘤所在之處。

And here we see the illustration of blocking the liver.

這張圖上可以看到擋住了肝臟。

The nanoparticles don't go there,

奈米粒子不會到那裡去，

and they instead end up in the tumor.

它們最後會到達腫瘤處。

So, sometimes, unexpected connections are made in science

有時，在科學中未預期的連結

that lead to new solutions.

反而會導致新的解決方案。

Another strategy for preventing nanoparticles

還有一種策略可以預防奈米粒子

from getting stuck in the liver

被困在肝臟中，

is to use the body's own nanoparticles.

那就是用身體自己的奈米粒子。

Yes -- surprise, surprise.

是的——好一個驚喜。

You, and you and you, and all of us have a lot of nanoparticles

你、你、你以及我們所有人

都有很多奈米粒子在體內循環著。

circulating in our bodies.

And because they're part of our bodies,

因為它們是我們身體的一部分，

the liver is less likely to label them as foreign.

肝臟不太可能會將它們 貼上外來物的標籤。

And these biological nanoparticles can be found in the saliva,

在唾液、血液、尿液、胰液中

in the blood, in the urine, in pancreatic juice.

都可以找到這些生物奈米粒子。

And we can collect them from the body

我們能從身體收集它們，

and use them as fire trucks for cancer drugs.

把它們當作消防車來運載抗癌藥物。

And in this case,

在這個情況下，肝臟中的 免疫細胞比較不可能

the immune cells in the liver are less likely to eat

會吞噬生物奈米粒子。

the biological nanoparticles.

So we're using a Trojan-horse-based concept

所以，我們用這個由 特洛伊木馬發想出來的概念

to fool the liver.

來欺騙肝臟。

And here we see the biological nanoparticles

在這裡可以看到生物奈米粒子

circulating in the blood.

在血液中循環。

They don't get recognized by the liver,

它們沒有被肝臟認出來，

and they end up in the tumor.

它們最後到達了腫瘤所在之處。

And in the future,

未來，

we want to exploit nature's own nanoparticles

我們想要利用大自然的奈米粒子

for cancer drug delivery,

來運輸抗癌藥物，

to reduce side effects and save lives

透過預防抗癌藥物跑錯地方，

by preventing the cancer drugs from being in the wrong location.

來減少副作用並拯救生命。

However, a major problem has been:

然而，一直有個重大的問題：

How do we isolate these biological nanoparticles in large quantities

我們要如何大量地將生物奈米粒子

在不破壞它們的前提下隔離出來？

without damaging them?

My lab has developed an efficient method for doing this.

我的實驗室已對此 開發出了有效的方法。

We can process large quantities of liquids from the body

我們可以處理大量的體液，

to produce a highly concentrated, high-quality formulation

來製成高濃度、高品質的

生物奈米粒子配方。

of biological nanoparticles.

And these nanoparticles are not yet in clinical use,

這些奈米粒子還沒有在臨床上使用，

because it takes an average of 12 years

因為平均要花十二年

to get something from the lab

才能把實驗室中的成果

to your medicine cabinet.

帶進你的藥櫃當中。

And this is the type of challenge that requires teamwork

這種挑戰

需要科學家和醫師的團隊合作，

from scientists and physicians,

who dedicate their lives to this battle.

將一生投入這場戰役。

And we keep going, thanks to inspiration from patients.

因為病人的鼓舞， 我們持續努力著。

And I believe that if we keep working on these nanomedicines,

我相信，如果我們繼續 在奈米醫學的領域奮鬥，

we will be able to reduce harm to healthy organs,

我們將能減少對健康器官的損害，

improve quality of life

改善生命品質，

and save future patients.

拯救未來的病人。

I like to imagine

我總會想，

that if these treatments had been available for Rebecca,

如果瑞貝卡當初能用這些治療方法，

that call from her

她打來的那通電話，

could have been an invitation

就可能是要邀請我

not to her funeral,

參加她的婚禮，而不是葬禮。

but her wedding.

Thank you.

謝謝。

(Applause)

（掌聲）