Minimally invasive molecular delivery into the brain using optical modulation of vascular permeability
Open accessAbstract
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.
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Ultrashort pulsed laser can induce transient leakage of blood plasma without compromising vascular integrity.
“without compromising vascular integrity, the ultrashort pulsed laser could induce transient leakage of blood plasma.”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [216]
Cites
Chronic optical access through a polished and reinforced thinned skull
Drew, P. J., Shih, A. Y., Driscoll, J. D., Knutsen, P. M., Blinder, P., Davalos, D., Akassoglou, K., Tsai, P. S., & Kleinfeld, D. (2010) · Nature Methods · doi:10.1038/nmeth.1530 · Cited by 406 · see citing works
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The blood–brain barrier: Structure, regulation and drug delivery
Wu, D., Chen, Q., Chen, X., Han, F., Chen, Z., & Wang, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01481-w · Cited by 1,906 · see citing works
“216 They combined the ultrashort pulsed laser with a systemic injection to deliver target molecules to brain cortex and different other tissues.”
MethodProgress in brain targeting drug delivery system by nasal route
Khan, A. R., Liu, M., Khan, M. W., & Zhai, G. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.09.001 · Cited by 402 · see citing works
Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy
Upton, D. H., Ung, C., George, S. M., Tsoli, M., Kavallaris, M., & Ziegler, D. S. (2022) · Theranostics · doi:10.7150/thno.69682 · Cited by 182 · see citing works
- Authors
- Choi, M., Ku, T., Chong, K., Yoon, J., & Choi, C.
- Affiliations
- Department of Bio and Brain Engineering,
- Graduate School of Medical Science and Engineering,
- Korea Advanced Institute of Science and Technology (KR)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-16
- Volume
- 108
- Issue
- 22
- Pages
- 9256-9261
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3107279
- OpenAlex
- W2119934083
- Cited by
- 59
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 1 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- blood-brain barrier, vascular permeability, ultrafast lasers, brain drug delivery, minimally invasive delivery, cerebral cortex, nanoparticles, viral vectors, chemical probes, calcium sensor
- MeSH terms
- Animals, Astrocytes, Brain, Calcium, Capillary Permeability, Fluorescent Dyes, Lasers, Light, Male, Mice, Inbred ICR, Microscopy, Fluorescence, Permeability, Photochemistry, Photons, Mice
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