BBB pathophysiology–independent delivery of siRNA in traumatic brain injury
Name
eabd6889.full.pdf
Description
Published version
Size
7.73 MB
Format
Adobe PDF
Checksum (MD5)
e73d5ee0c8960e45e238f2496ce37e26
Author(s)
Li, Wen
Qiu, Jianhua
Li, Xiang-Ling
Aday, Sezin
Zhang, Jingdong
Conley, Grace
Xu, Jun
Joseph, John
Lan, Haoyue
Langer, Robert
Date Issued
2021
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Version
Final published version
Abstract
Copyright © 2021 The Authors, some rights reserved. Small interfering RNA (siRNA)–based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology–independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/sciadv.abd6889
