爆炸的纳米气泡可以杀死癌细胞

Exploding nanobubbles can kill cancer cells

 

By Robert F. ServiceFeb. 15, 2016

　

 

图示：成簇的金纳米粒子位于癌细胞表面。当受到红外光的冲击时，这些水团就会蒸发附近的水，产生水汽泡，这些水汽泡会爆裂并撕裂细胞。

　

　

一项新的纳米技术研究表明，金原子簇（Cluster of gold）可以检测并杀死肿瘤切除手术后遗留下来的癌细胞。

 

目前，这种方法只在少数老鼠身上试验过。但研究人员正在设计一项临床试验，可能在未来两年内开始在人体上测试这种疗法。如果这项技术在人体上被证明是成功的，它将大大提高癌症患者的康复几率，特别是在手术切除整个肿瘤是不可能的情况下。

 

当外科医生给癌症病人做手术时，他们会尽最大的努力移除最后的病变细胞，因为任何遗留下来的细胞都可能长出新的肿瘤或在全身转移。肿瘤医生通常会在手术后进行放疗或化疗，以增加消除任何残留肿瘤细胞的机会。但这种对抗癌症的标准方法绝不是万无一失的。

 

近年来，内科医生和科学家都在寻求纳米技术的帮助。德克萨斯州休斯顿莱斯大学和其他地方的研究人员在过去十年中率先采用了一种方法，这种方法表明，被称为纳米颗粒的金原子簇可以作为对抗癌细胞的有力武器。实体癌症肿瘤通常有漏的血管。因此，当黄金纳米颗粒被注入血液时，它们往往会从血管开口渗出，聚集在肿瘤周围。为了清理周围环境，这些细胞通常会吞噬纳米颗粒。但是一旦进入细胞内，纳米颗粒就会起到特洛伊木马（Trojan horses）的作用。当研究人员用能够穿透几厘米组织的红外线激光击中金原子时，这些微粒就会升温并杀死癌细胞。

　

 

不幸的是，纳米颗粒加热策略有两个问题，Dmitri Lapotko说，他以前是Rice的物理学家，现在是Masimo公司的激光科学主管，Masimo公司是一家位于加州欧文的医学纳米技术公司。首先，一些金纳米颗粒必然会进入正常细胞内或周围，因此当激光治疗癌症时，健康的组织可能会受损。同样，通常用于加热粒子的激光会发射连续的红外光束。这也将热量从癌细胞扩散到正常组织。如果肿瘤生长在重要组织内或周围，如神经或动脉壁，任何对健康组织的间接损害都可能使人衰弱或危险。

 

为了缩小治疗的范围，Lapotko和他的同事们试图修改消灭纳米颗粒的方法。他们从植入人类鳞状细胞癌的小鼠开始，鳞状细胞癌是人类头颈部肿瘤中常见的癌细胞，用标准疗法治疗尤其困难。他们用免疫蛋白抗体装饰黄金纳米颗粒，这种抗体专门附着在鳞状细胞表面的受体上。这就浓缩了这些粒子，在癌细胞内部和周围形成了几十个粒子簇。研究人员只发射了超短的红外脉冲，而没有发射连续的激光束。

　

 

正如所希望的那样，这阻止了热量扩散到周围的正常组织。但这种方法产生了更重要的影响:在有大量金纳米颗粒的地方，温度会上升得更高。这些蒸发的相邻的水分子，产生微小的气泡，迅速膨胀和破裂，撕裂癌细胞。Lapotko说，关键在于“纳米粒子群在癌细胞中产生纳米气泡，而不是在正常组织中。”

 

拉波特科和他的同事们在《自然纳米技术》网站上报道说，这些微小的爆炸不仅使人们能够从肿瘤细胞所在的位置接收到声音，从而检测到只有3个癌细胞的存在，而且还在这个过程中摧毁了这些细胞。在手术切除大部分癌细胞的情况下，100%的动物存活了下来，这多亏了没有残留的癌细胞存活。如果只能选择部分切除肿瘤，动物的存活率就会翻倍。

 

“这非常非常有趣，”休斯顿德克萨斯大学MD安德森癌症中心的Mien-Chie Hung说。洪教授指出，这种方法与传统手术非常吻合，传统手术可以切除大的肿瘤，但不能识别残留的癌细胞。他说，这项新技术的作用就像显微手术，瞄准那些残留的细胞。洪强调说，许多在动物身上起作用的肿瘤学方法在人类身上的效果从来都不一样。但是如果这个成功了，它将会打开一扇全新的窗户来发现和清除术后残留的癌细胞。

 

Exploding nanobubbles can kill cancer cells

　

By Robert F. ServiceFeb. 15, 2016 , 11:00 AM

　

Clusters of gold atoms can detect and kill cancer cells commonly left behind after tumor-removal surgery, according to a study of a new nanotechnology technique. For now, the approach has only been tried in a handful of mice. But the researchers are designing a clinical trial that could begin testing the therapy in humans in the next 2 years. If the technique proves successful in people, it could dramatically improve the odds for cancer patients, particularly in cases where surgically removing an entire tumor is impossible.

 

When surgeons operate on cancer patients, they do their best to remove every last diseased cell, because any left behind can grow into new tumors or metastasize throughout the body. Oncologists then typically follow up surgery with either radiation treatments or chemotherapy to increase the chances of eliminating any residual tumor cells. But this standard approach to fighting cancer is anything but foolproof.

 

In recent years, physicians and scientists have looked to nanotechnology for help. One approach pioneered over the last decade by researchers at Rice University in Houston, Texas, and elsewhere has shown that clusters of gold atoms known as nanoparticles can serve as a potent weapon against cancer cells. Solid cancer tumors typically have leaky blood vessels. As a result, when gold nanoparticles are injected into the bloodstream, they tend to seep out of the vessel openings and congregate around tumors. To clean up their surroundings, those cells then often engulf the nanoparticles. But once inside the cells, the nanoparticles can act as Trojan horses. When researchers hit the gold atoms with infrared laser light, which can travel through centimeters of tissue, the particles heat up and kill the cancer cells.

 

Unfortunately, the nanoparticle heater strategy has two problems, says Dmitri Lapotko, a physicist formerly with Rice and now head of laser science at Masimo Corporation, a medical nanotechnology company in Irvine, California. The first is that some gold nanoparticles invariably end up in and around normal cells, so healthy tissue can get damaged when the lasers go after cancers. As well, the lasers that are normally used for heating the particles fire continuous beams of infrared light. This too spreads the heat far beyond cancer cells and into the normal tissue. In cases where tumors grow in and around vital tissues, such as nerves or arterial walls, any collateral damage to healthy tissues can be debilitating or dangerous.

 

In an effort to narrow the therapy’s focus, Lapotko and colleagues sought to modify the approach to zapping nanoparticles. They started with mice that had been implanted with human squamous cell carcinoma, cancer cells common in human head and neck tumors that are particularly difficult to treat with standard therapies. They decorated their gold nanoparticles with immune protein antibodies, which specifically latch onto receptors that sit on the surface of squamous cells. That concentrated the particles, creating clusters of dozens of them in and around cancer cells. And instead of firing continuous laser beams, the researchers fired only ultrashort infrared pulses.

 

As hoped, this prevented the heat from spreading to surrounding normal tissues. But the approach had an even more important effect: It caused temperatures to rise higher where there were large clusters of gold nanoparticles. This vaporized adjacent water molecules, creating tiny bubbles that quickly expand and burst, ripping apart the cancer cells. They key, Lapotko says, is that “nanoparticle clusters produce nanobubbles in cancer cells and not normal tissue.”

 

Online today inNature Nanotechnology, Lapotko and his colleagues report that those mini-explosions made it possible not only to pick up sound from where tumor cells were located—and thereby detect the presence of as few as three cancer cells—but it also destroyed the cells in the process. For cases in which it was possible to surgically resect most of the cancer tissue, 100% of the animals survived, thanks to the fact that no residual cancer cells remained alive. And in cases where only partial surgical removal of a tumor was an option, the survival rate for the animals doubled.

 

“This is very, very interesting,” says Mien-Chie Hung of the University of Texas MD Anderson Cancer Center in Houston, who is exploring treating tumors with nanoparticles. Hung notes that the approach dovetails very well with conventional surgery that is able to remove large tumors but is unable to identify cancer cells that remain behind. The new technique, he says, acts like microscopic surgery to target those residual cells. Hung emphasizes that many oncology approaches that work in animals never wind up as effective in humans. But if this one does, it could open a whole new window into spotting and eliminating residual cancer cells left behind after surgery.

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Clusters of gold nanoparticles sit on the surface of a cancer cell. When hit with a burst of infrared light, the clusters vaporize nearby water, creating bubbles of vapor that burst and tear apart the cell.

Clusters of gold nanoparticles sit on the surface of a cancer cell. When hit with a burst of infrared light, the clusters vaporize nearby water, creating bubbles of vapor that burst and tear apart the cell. D. S. WAGNER ET AL., BIOMATERIALS, 31 (2010)

 

http://www.sciencemag.org/news/2016/02/exploding-nanobubbles-can-kill-cancer-cells