利用血管通透性的光调节实现微创分子递送至大脑。
Minimally invasive molecular delivery into the brain using optical modulation of vascular permeability.
机构信息
Department of Bio and Brain Engineering, KI for the BioCentury, and Optical BioImaging Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
出版信息
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9256-61. doi: 10.1073/pnas.1018790108. Epub 2011 May 16.
Abstract
Systemic delivery of bioactive molecules in the CNS is hampered by the blood-brain barrier, which has bottlenecked noninvasive physiological study of the brain and the development of CNS drugs. Here we report that irradiation with an ultrashort pulsed laser to the blood vessel wall induces transient leakage of blood plasma without compromising vascular integrity. By combining this method with a systemic injection, we delivered target molecules in various tissues, including the brain cortex. This tool allows minimally invasive local delivery of chemical probes, nanoparticles, and viral vectors into the brain cortex. Furthermore, we demonstrated astrocyte-mediated vasodilation in vivo without opening the skull, using this method to load a calcium indicator in conjunction with label-free photoactivation of astrocytes.
摘要
血脑屏障阻碍了生物活性分子在中枢神经系统中的系统性传递，这也阻碍了对大脑的非侵入性生理研究和中枢神经系统药物的发展。在这里，我们报告称，用超短脉冲激光辐照血管壁会引起血浆的瞬时渗漏，而不会损害血管完整性。我们将这种方法与系统注射相结合，将目标分子递送到包括大脑皮层在内的各种组织中。该工具允许将化学探针、纳米颗粒和病毒载体等以微创的方式递送到大脑皮层。此外，我们还证明了使用这种方法无需打开颅骨，即可在体内实现星形胶质细胞介导的血管扩张，从而将钙指示剂与星形胶质细胞的无标记光激活相结合进行负载。
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本文引用的文献
1
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Nat Methods. 2010 Dec;7(12):981-4. doi: 10.1038/nmeth.1530. Epub 2010 Oct 21.
2
Comparison of label-free biosensing in microplate, microfluidic, and spot-based affinity capture assays.无标记生物传感在微孔板、微流控和点样亲和捕获分析中的比较。
Anal Biochem. 2010 Oct 1;405(1):1-10. doi: 10.1016/j.ab.2010.06.009. Epub 2010 Jun 8.
3
Laser tricks without labels.无标记的激光技巧。
Nat Methods. 2010 Apr;7(4):261-6. doi: 10.1038/nmeth0410-261.
4
Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window.通过慢性颅骨视窗对小鼠新皮层进行长期、高分辨率成像。
Nat Protoc. 2009;4(8):1128-44. doi: 10.1038/nprot.2009.89. Epub 2009 Jul 16.
5
Femtosecond laser disruption of subcellular organelles in a living cell.飞秒激光对活细胞中亚细胞器的破坏
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6
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7
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Brain Res. 2008 Oct 9;1234:198-205. doi: 10.1016/j.brainres.2008.07.121. Epub 2008 Aug 12.
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