ACS Nano：siRNA首次实现癌细胞内传输

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2009-9-14 9:17:28
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ACS Nano：siRNA首次实现癌细胞内传输7 C. G* |* ^$ S: l  ~  f

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. ?6 M: l0 {. S) G4 T美国加州大学圣巴巴拉分校（UCSB）的研究人员开发出一种新方法：通过简单地将癌细胞暴露在非损伤性激光中的方法，即可将药物释放到癌细胞中。此项研究成果发表在美国化学学会主办的《纳米科技》杂志上。7 J2 ^0 |* {  a4 i- S4 [  G
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论文主要作者，UCSB化学和生物化学系教授诺伯特·雷奇认为，此一全新工具将使生物学家得以研究当一个基因打开或关闭时，这些基因是如何发挥作用的。一言以蔽之，科学家所描述的在细胞内控制基因的能力，只需简单到将其暴露在非损伤性激光中即可实现。3 p8 _: j% h6 V. v! ]

) A9 S$ A: B- F5 m) iUCSB的科学家在培养皿中将来自小鼠的癌细胞进行培养，然后引入具有肽脂涂层的金纳米壳，并封装成可被细胞吸收的药物siRNA，最后再将细胞暴露在非损伤性的红外激光中。由此，研究人员首次实现了这种强大的siRNA药物在哺乳动物癌细胞内的传输，将这种内化纳米粒子在一束近红外激光（调谐至能以一种特定的空间模式实现峰值吸收）中暴露数秒钟，药物即可释放。
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8 F: _, s0 d8 Z* j/ m  Y研究人员表示，该项技术的难点在于如何将多种生物化学成分与可被细胞吸收的紧凑纳米粒子相结合，并稳定地存在，直到其按照需要进行释放。激光控制释放是一个方便而强大的工具，允许对特定细胞释放出精确剂量的药物。近红外光的生物友好型组织渗透法对于将这种能力扩展到较大的生物系统来说是十分理想的。该技术亦可扩展到针对不同的生物目标释放不同的药物分子。* g' }9 M. b9 D( q+ ^+ |

. C7 H6 N. L  P6 L' N# {. G" T原始出处：
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* U3 u* u0 S2 }/ V- }! \, oACS Nano, 2009, 3 (7), pp 2007–2015 DOI: 10.1021/nn900469q
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* B; n6 h$ H9 g; qLaser-Activated Gene Silencing via Gold Nanoshell-siRNA Conjugates
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Gary B. Braun?, Alessia Pallaoro?, Guohui Wu?, Dimitris Missirlis?, Joseph A. Zasadzinski?, Matthew Tirrell? and Norbert O. Reich?*4 m& p  s/ A5 O! h
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Department of Chemistry and Biochemistry
5 v8 U7 W# ]5 Q Department of Chemical Engineering and Materials Research Laboratory, University of California, Santa Barbara, California 93106, e9 V+ D# r& H/ A) u# [. N

% P& Z. M, u3 jThe temporal and spatial control over the delivery of materials such as siRNA into cells remains a significant technical challenge. We demonstrate the pulsed near-infrared (NIR) laser-dependent release of siRNA from coated 40 nm gold nanoshells. Tat-lipid coating mediates the cellular uptake of the nanomaterial at picomolar concentration, while spatiotemporal silencing of a reporter gene (green fluorescence protein) was studied using photomasking. The NIR laser-induced release of siRNA from the nanoshells is found to be power- and time-dependent, through surface-linker bond cleavage, while the escape of the siRNA from endosomes occurs above a critical pulse energy attributed to local heating and cavitation. NIR laser-controlled drug release from functional nanomaterials should facilitate more sophisticated developmental biology and therapeutic studies.