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wo357026239

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In previous works, the dye exclusion method was used to examine cell death. Under this circumstance, the laser powers applied have to be high enough to compromise the cell membrane and induce instant cell death (necrosis). When a cell is labeled with gold nanoparticles, heat can be built up around the nanoparticles
instantly upon the irradiation of an ultrafast pulsed laser. If the laser power density is high enough, fragmentation of gold nanoparticles can be produced,which can bring a localized mechanical shock to the cell membrane causing membrane perforation. At a low power, when the energy fluence is high enough, the heat produced from gold nanorods can also burn the cell membrane. These two effects will compromise the integrity and cause leaking of cell membrane, leading to rapid cell death.As known, cell proliferation can be stopped either by damaging the cells (necrosis) or by inducing cell apoptosis. Necrosis is a process of cell death by
accident, which is normally due to the compromising of membrane integrity. In contrast, apoptosis is programmed cell death (suicide), which is a natural process that governs the proliferation of cells in a living body. As a matter of fact, what makes a cell cancerous is the disturbance of its natural apoptosis, leading to its proliferation out of control. To restore and enhance apoptosis, certain stimuli such as drugs and irradiation can be introduced. This forms the basis of the conventional chemotherapy and radiation therapy. With reduction in power density or energy fluence, the thermal effect becomes dominant. While keeping the membrane integrated, the photothermal effect of gold nanorods can potentially lead to the dysfunction of the subcellular structures that govern the proliferation of cells, causing cell apoptosis .While maintaining the therapeutic effects, a laser operating at these lower energy levels is clinically safer. In addition, compared with necrosis, apoptosis is more suitable to in vivo treatment since inflammation and even secondary cancers associated with necrosis can be avoided. Despite its significance, laser induced apoptosis of cancer cells in the presence of gold nanoparticles has not been investigated, to the best of our knowledge.
       In this work, gold nanorod-enhanced two-photon luminescence imaging and apoptosis of cancer cells will be investigated in the aim of developing a way for efficient and medically safe cancer detection and microsurgery using femtosecond lasers under twophoton microscopy. A two-photon Fluoview inverted scanning
microscope was used for two-photon excitation of gold nanorods. A human cervical cancer cell line HeLa was used as a model. To achieve efficient targeting of gold nanorods to the cancer cells, transferrin molecules were conjugated to the surface of the nanorods. Transferrin has been proven to be efficient in enhancing
cancer targeting by nanoparticles including gold nanoparticles.The imaging capability of gold nanorods was also compared with the cell autofluorescence and molecular dyes.

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weichin

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爱与雨下(金币+1): 2012-01-04 08:50:28
wo357026239(金币+70, 翻译EPI+1): 2012-01-05 12:08:50
供参考:
    在以往的研究中,染色排除法被用于研究细胞死亡。在这种情况下,所应用的激光功率必须高到足以破坏细胞膜并诱导瞬间细胞死亡(坏死)。当用黄金纳米粒子标记一个细胞时,超快脉冲激光照射后会即刻在纳米粒子周围产生热量。如果激光功率强度足够高,可实现黄金纳米粒子的分裂,从而给细胞膜带来局部机械冲击,造成穿孔。在低功率调节下,当能注量足够高时,金纳米棒产生的热量也还可以烧毁细胞膜。这两种效应都会破坏完整性并造成细胞膜的泄漏,导致细胞快速死亡。众所周知,通过破坏细胞(坏死)或诱导细胞凋亡均可阻止细胞增殖。坏死通常是由于细胞膜的完整性被破坏而造成的意外细胞死亡过程。与此相反,细胞凋亡则是程序性细胞死亡(自杀),这是一个控制活体细胞增殖的自然过程。事实上,细胞之所以发生癌变,是因为自然细胞凋亡遭到干扰,从而导致其增殖失控。可以利用诸如药物和辐射等刺激因素,以恢复和提高细胞凋亡。这就是传统化疗和放射疗法的基础。随着功率强度和能注量的减少,热效应占据主导地位。在保持细胞膜完整的前提下,金纳米棒的光热效应有可能致使支配细胞增殖的亚细胞结构功能失调,引起细胞凋亡。在保证同样治疗效果的同时,在较低能量水平上运行的激光在临床上更加安全。此外,较之坏死,凋亡更适合于体内治疗,因为可以避免炎症和坏死引起的继发性癌症。据我们所知,尽管黄金纳米粒子协同下激光诱导的癌细胞凋亡的意义极其重大,却鲜有人对其开展研究。
    在本研究工作中,将对金纳米棒增强的双光子荧光成像和癌细胞凋亡开展研究,以期利用双光子显微镜下飞秒激光器开发一种有效、安全的癌症检测手段。利用双光子FluoView倒置扫描显微镜实现金纳米棒的双光子激发。用宫颈癌HeLa细胞系作测试模型。将转铁蛋白分子结合于纳米棒表面,以实现金纳米棒高效锁定靶癌细胞。已经证明,转铁蛋白可以促进纳米粒子(包括金纳米粒子)锁定靶癌细胞。同时,也对金纳米棒的成像能力和细胞自体荧光及分子燃料进行了比较。
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2楼2012-01-03 21:47:05
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