@article{1a843f9d5e76479a81de209c4f76c265,
title = "Reversibly Modulating the Blood-Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles",
abstract = "The blood-brain barrier (BBB) is highly selective and acts as the interface between the central nervous system and circulation. While the BBB is critical for maintaining brain homeostasis, it represents a formidable challenge for drug delivery. Here we synthesized gold nanoparticles (AuNPs) for targeting the tight junction specifically and demonstrated that transcranial picosecond laser stimulation of these AuNPs post intravenous injection increases the BBB permeability. The BBB permeability change can be graded by laser intensity, is entirely reversible, and involves increased paracellular diffusion. BBB modulation does not lead to significant disruption in the spontaneous vasomotion or the structure of the neurovascular unit. This strategy allows the entry of immunoglobulins and viral gene therapy vectors, as well as cargo-laden liposomes. We anticipate this nanotechnology to be useful for tissue regions that are accessible to light or fiberoptic application and to open new avenues for drug screening and therapeutic interventions in the central nervous system.",
keywords = "blood-brain barrier, gold nanoparticle, therapeutics delivery, tight junction targeting",
author = "Xiaoqing Li and Vamsidhara Vemireddy and Qi Cai and Hejian Xiong and Peiyuan Kang and Xiuying Li and Monica Giannotta and Hayenga, {Heather N.} and Edward Pan and Shashank Sirsi and Celine Mateo and David Kleinfeld and Chris Greene and Matthew Campbell and Elisabetta Dejana and Robert Bachoo and Zhenpeng Qin",
note = "Funding Information: The authors thank the Histo Pathology Core at University of Texas Southwestern Medical Center (UTSW) for assistance with histology staining, Dr. Bret Evers for assistance with H&E analysis, the Electron Microscopy Core of UTSW for assistance with EM sample processing, Yaning Liu and Dr. Haihang Ye for assistance with EM imaging of gold nanoparticles, Xueqi Xu for assistance with liposome synthesis, Dr. Stephanie Shiers for assistance with NeuN and Ankyrin-G staining, Dr. Susanne J. van Veluw and Dr. Steven S. Hou for providing the code of vasomotion analysis, and members of the Qin laboratory for discussions. This research was funded by Cancer Prevention and Research Institute of Texas (CPRIT) grants RP160770 and RP190278 received by Z.Q., an American Heart Association Collaborative Sciences Award (19CSLOI34770004) received by Z.Q., the National Institutes of Health grant 1S10OD021685-01A1 received by the Electron Microscopy Core of UTSW, the European Research Council (project EC-ERC-VEPC, contract 742922) received by E.D., a Fondazione CARIPLO Foundation grant (2016-0461) received by M.G., and a European Research Council (ERC: Retina-Rhythm); Science Foundation Ireland (SFI) (12/YI/B2614 and 155 11/PI/1080); The Irish Research Council (IRC); The Health Research Board of Ireland (HRB); an SFI Centres grant supported in part by a research grant from SFI under grant number 16/RC/3948 and co-funded under the European Regional Development fund by FutureNeuro industry partners received by M.C. Publisher Copyright: {\textcopyright} ",
year = "2021",
month = nov,
day = "24",
doi = "10.1021/acs.nanolett.1c02996",
language = "English (US)",
volume = "21",
pages = "9805--9815",
journal = "Nano Letters",
issn = "1530-6984",
publisher = "American Chemical Society",
number = "22",
}