康奈尔大学：超细纳米颗粒以不同寻常的方式杀死癌细胞

Cornell Uiversity: Ultrasmall nanoparticles kill cancer cells in unusual way

　

由Catharine Paddock博士于2016年9月29日星期四发表

科学家们惊奇地发现，原本用来点亮外科手术肿瘤的荧光纳米颗粒也可以通过引发一种罕见的细胞死亡来杀死癌细胞。

　

　

 

图示：人类癌症细胞

 

这种超细的粒子通过从周围环境中吸收铁并将其输送到癌细胞中来杀死癌细胞。这个过程被称为铁死亡（Ferroptosis）），它使细胞膜破裂。

 

他们在《自然纳米技术》杂志上报道了这一发现，以及他们如何在细胞培养和小鼠中测试纳米颗粒。

 

首席研究员之一、纽约伊萨卡康奈尔大学(Cornell University)工程学教授乌尔里希·维斯纳(Ulrich Wiesner)说:

“如果你必须设计出一种可以杀死癌症的纳米颗粒，那么这就是你要做的事情。”

 

纳米粒子是一种至少一维小于100纳米的微小粒子。与大规模使用同一种材料相比，它们具有不同寻常的特性，科学家和工程师正在将它们应用于许多领域，包括电子和生物医学。

 

这项新研究的核心的纳米颗粒被称为康奈尔点(Cornell dots)，是一种荧光二氧化硅微粒，直径为5纳米。

　

　

 

它们最初是由威斯纳教授在10多年前开发出来，作为癌症外科手术的工具。它们附着在癌细胞上，并点亮它们，这样外科医生就能看到在哪里切除。

 

这些颗粒还打算用于靶向药物输送和环境传感。

“内在治疗属性”

 

新的研究表明，瞄准癌症的康奈尔点可以杀死癌细胞，而不需要携带药物。

第一作者Michelle Bradbury，纽约纪念斯隆凯特琳癌症中心的术中成像主任，说:

“事实上，这是我们首次证明这种粒子具有内在的治疗特性。”

 

威斯纳教授解释说:“在正常健康的组织中，这种颗粒的耐受性很好，但一旦你有了肿瘤，在非常特殊的条件下，这些颗粒就会成为杀手。”

 

研究人员发现了康奈尔点的抗癌特性，当时他们正试图找出大浓度的药物的耐受性。他们在几年里进行了几次试验。

 

然后，令他们惊讶的是，他们发现，当高剂量的肽涂层康奈尔点与癌细胞孵育时——尤其是当细胞缺乏营养时——这些颗粒从环境中吸收铁并将其传递到癌细胞中。

 

将铁输送到细胞中会引发一种叫做铁死亡（ferroptosis）的细胞死亡，它会使细胞膜破裂。这与通常观察到的分裂细胞死亡即细胞凋亡不同。

　

　

 

“Wave of destruction攻击波”

威斯纳教授说，在接触康奈尔点之后的24-48小时内，他们观察到一股“破坏浪潮”如何席卷了整个癌细胞培养过程。

 

在进一步的实验中，他们给移植了黑色素瘤肿瘤的老鼠注射了高剂量的康奈尔涂层点，发现他们在没有引起任何不良反应的情况下缩小了肿瘤。

 

作者总结他们的发现表明:“铁死亡可以被超细二氧化硅纳米颗粒可以靶向控制，并且可能具有治疗潜力。”

 

“我们发现了另一种迄今为止人们还没有想到的工具。这改变了我们对纳米粒子的看法，也改变了它们的潜在用途。”

乌尔里希威斯纳教授说。

 

研究人员现在计划测试康奈尔点和其他标准疗法在不同种类癌症肿瘤中的作用。

他们希望在开始人体试验前使其更有效。该团队还将探索如何调整粒子以针对特定癌症类型。

 

Ultrasmall nanoparticles kill cancer cells in unusual way

Published      Thursday 29 September 2016 By Catharine Paddock PhD     

Scientists are surprised to find that ultrasmall, fluorescent nanoparticles - originally developed to light up tumors for surgery - can also kill cancer cells by triggering a type of cell death that is not commonly observed.

Human cancer cell

The ultrasmall particles kill cancer cells by taking iron from their environment and delivering it into them. The process - called ferroptosis - ruptures the cell's membrane.

They report the discovery - and how they tested the nanoparticles in cell cultures and mice - in the journal Nature Nanotechnology.

 

One of the lead investigators, Ulrich Wiesner, a professor of engineering at Cornell University in Ithaca, NY, says:

 

"If you had to design a nanoparticle for killing cancer, this would be exactly the way you would do it."

 

Nanoparticles are tiny particles with at least one dimension no bigger than 100 nanometers. They have unusual properties compared with the same material on a larger scale, and scientists and engineers are applying them in many fields, including electronics and biomedicine.

 

The nanoparticles at the center of the new study - called Cornell dots, or C dots - are ultrasmall, fluorescent silica particles, with a diameter of 5 nanometers.

 

They were originally developed by Prof. Wiesner over 10 years ago as a tool for cancer surgery. They attach to cancer cells and light them up so surgeons can see where to cut.

 

The particles were also intended to be used for targeted drug delivery and environmental sensing.

 

'Intrinsic therapeutic properties'

The new study shows that the cancer-targeting Cornell dots can kill cancer cells without having to carry drugs.

 

Lead author Michelle Bradbury, director of intraoperative imaging at Memorial Sloan Kettering Cancer Center in New York, NY, remarks:

 

"In fact, this is the first time we have shown that the particle has intrinsic therapeutic properties."

 

"The particle is well tolerated in normally healthy tissue," Prof. Wiesner explains, "but as soon as you have a tumor, and under very specific conditions, these particles become killers."

 

The researchers discovered the cancer-killing properties of the Cornell dots when they were trying to find out how well large concentrations could be tolerated. They carried out several experiments over several years.

 

Then, to their surprise, they found that when high doses of peptide-coated Cornell dots were incubated with cancer cells - and particularly when the cells were starved of nutrients - the particles took iron from the environment and delivered it into the cancer cells.

 

Delivering iron into the cells triggers a type of cell death called ferroptosis, which ruptures the cell membrane. This is different to the more commonly observed fragmentation cell death known as apoptosis.

 

 

'Wave of destruction'

Prof. Wiesner says only 24-48 hours after exposure to the Cornell dots, they observed how a "wave of destruction" swept through the entire cancer cell culture.

 

In further experiments they injected high doses of the coated Cornell dots into mice grafted with melanoma tumors and found they shrank the tumors without causing any adverse reactions.

 

The authors conclude their findings show "ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential."

 

"We've found another tool that people have not thought about at all so far. This has changed our way of thinking about nanoparticles and what they could potentially do."

Prof. Ulrich Wiesner

The researchers now plan to test how the Cornell dots work with other standard therapies in different kinds of cancer tumors.

 

They want to make them more effective before starting tests in humans. The team will also be exploring ways to tailor the particles to target specific cancer types.

https://www.medicalnewstoday.com/articles/313181.php