Myunghwan Choia, Taeyun Kub, Kyuha Chongb, Jonghee Yoona, and Chulhee Choia,b,c,d,1
aDepartment of Bio and Brain Engineering,
bGraduate School of Medical Science and Engineering,
cKI for the BioCentury, and
dOptical BioImaging Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
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.
femtosecond pulsed laser, laser tissue interaction, molecular delivery, permeability
1 To whom correspondence should be addressed.
Author contributions: M.C. and C.C. designed research; M.C., T.K., K.C., and J.Y. performed research; M.C., T.K., K.C., J.Y., and C.C. analyzed data; and M.C. and C.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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