nanosurface 2008-05-09 22:29
科学家用纳米“虫子”靶向肿瘤Researchers target tumors with tiny 'nanoworms'
[b][color=Blue]【纳米科技世界快讯】Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors.[/color][/b]
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[color=DimGray]Segmented “nanoworms” composed of magnetic iron oxide and coated with a polymer are able to find and attach to tumors. Credit: Ji-Ho Park, UCSD[/color]
Their discovery, detailed in this week’s issue of the journal Advanced Materials, is reminiscent of the 1966 science fiction movie, the Fantastic Voyage, in which a submarine is shrunken to microscopic dimensions, then injected into the bloodstream to remove a blood clot from a diplomat’s brain.
Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.
“Most nanoparticles are recognized by the body's protective mechanisms, which capture and remove them from the bloodstream within a few minutes,” said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”
“When attached to drugs, these nanoworms could offer physicians the ability to increase the efficacy of drugs by allowing them to deliver them directly to the tumors,” said Sangeeta Bhatia, a physician, bioengineer and a professor of Health Sciences and Technology at MIT who was part of the team. “They could decrease the side effects of toxic anti-cancer drugs by limiting their exposure of normal tissues and provide a better diagnosis of tumors and abnormal lymph nodes.”
The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.
“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”
In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.
“Because of its elongated shape, the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface,” said Sailor. “And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.”
The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours.
“This is an important property because the longer these nanoworms can stay in the bloodstream, the more chances they have to hit their targets, the tumors,” said Ji-Ho Park, a UC San Diego graduate student in materials science and engineering working in Sailor’s laboratory.
Park was the motivating force behind the discovery when he found by accident that the gummy worm aggregates of nanoparticles stayed for hours in the bloodstream despite their relatively large size.
While it’s not clear yet to the researchers why, Park notes that “the nanoworm’s flexibly moving, one dimensional structure may be one the reasons for its long life in the bloodstream.”
The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.
“We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,” said Ruoslahti. We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.”
Source: University of California - San Diego
nanosurface 2008-05-13 03:08
给个中文翻译版
目前，美国加州大学圣地亚哥分校、圣芭芭拉分校以及麻省理工学院的科学家们研制出一种纳米等级大小的“纳米蠕虫”，它可以在不破坏人体正常免疫防御系统前提下在血流中巡游，就像一个微型抗癌导弹，能够破坏“肿瘤细胞基地”。
这项研究发现发表在本周出版的《先进材料》（Advanced Materials）杂志上，纳米蠕虫不由得让人们想起了1966年的科幻电影《神奇航行》，片中一艘潜艇缩小至显微镜观测等级大小，然后科学家将这个微型潜艇注射到血液中，潜艇摧毁了一位高级官员大脑中的血栓。目前，使用纳米蠕虫医师将最终能够定位和移除常规医学方法中难以探测的小型肿瘤细胞。通过载荷可以消除肿瘤的特殊药物，这种超微纳米工具有朝一日可以有效地向肿瘤送递高浓度对人体有毒的抗癌药物，同时对人体其他器官不会产生负面影响。
领导此项研究的加州大学圣地亚哥分校生物化学家迈克尔•塞勒教授说，“许多纳米微粒被认为是人体的保护机制，它可以在几分钟内在血液中捕捉并移除肿瘤细胞。它们之所以工作效率如此高，是由于其特殊外型和表面的聚合体外层可使纳米蠕虫可以规避人体机理对其的排斥特性。现在这种纳米蠕虫可以在人体内巡航数小时进行搜寻工作。”
该研究小组成员之一的麻省理工学院健康科学技术系生物学医师桑格塔•博哈蒂亚教授说，“当纳米蠕虫表面附加药物时，可提高药物的效力，对肿瘤细胞产生直接的摧毁消灭作用。这种方法还降低了有毒抗癌药物对正常组织所产生的副作用，以及提供对肿瘤和反常淋巴结更好的诊断。”
科学家们认为这种球形氧化铁纳米蠕虫连接在一起，就像一条蚯蚓的片断，可形成30纳米长（正常蚯蚓长度的300万分之一）粘性蠕虫状结构。纳米蠕虫的氧化铁成份可在诊断设备中发亮，尤其便于核磁共振成像（MRI）装置通过发现纳米蠕虫来寻找人体内的肿瘤细胞。塞勒称，纳米蠕虫的氧化铁成份具有超顺磁性特性，在核磁共振成像装置下将非常明亮。每个纳米蠕虫具有8个氧化铁磁性片断，这些磁性片断结合在一起将提供一个更大的观测信号。这样能够更好地观测更微小的肿瘤细胞，有望使医师能够诊断出处于早期发展阶段的癌症病情。
纳米蠕虫的聚合体外层是由右旋糖苷生物高聚物制成，科学家们使用治疗瘤细胞的F3缩氨酸分子涂在蠕虫外表。F3缩氨酸分子是由加州大学圣芭芭拉分校伯纳姆医学研究协会细胞生物学家厄基•劳斯拉蒂教授在实验室研制成功的，这种缩氨酸分子可使纳米蠕虫摧毁瘤细胞宿体。
塞勒说，“由于它的伸长外型，纳米蠕虫可以携带许多F3缩氨酸分子同时作用于瘤细胞表面，纳米蠕虫的联合效应可显著提高纳米摧毁瘤细胞的能力。”
科学家在他们的实验中对患有肿瘤的老鼠血液中注射纳米蠕虫，进一步检验了纳米蠕虫能够集合在肿瘤细胞，他们发现纳米蠕虫能够停留在血液中数小时。在塞勒实验室参加研究的材料科学和工程系研究生吉霍•帕克说，“这是一个重要的特性，纳米蠕虫能够更长时间地停留在血液中，这增大了摧毁打击肿瘤细胞的概率。”
劳斯拉蒂说，“我们目前使用纳米蠕虫构筑新一代智能瘤细胞摧毁纳米设备，我们希望未来这种设备将提高癌症诊断成像，并能够精确治疗癌瘤细胞。”
来源：新浪科技 魏冬