Delivery of High Mobility Group Box-1 siRNA Using Brain-Targeting Exosomes for Ischemic Stroke Therapy
- Authors
- Kim, Min kyung; Kim, Gyeungyun; Hwang, Do Won; Lee, Minhyung
- Issue Date
- Dec-2019
- Publisher
- AMER SCIENTIFIC PUBLISHERS
- Keywords
- Exosome; Rabies Virus Glycoprotein (RVG) Peptide; High Mobility Group Box 1 (HMGB1); Small Interfering RNA (siRNA); Ischemic Stroke
- Citation
- JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v.15, no.12, pp.2401 - 2412
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
- Volume
- 15
- Number
- 12
- Start Page
- 2401
- End Page
- 2412
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4480
- DOI
- 10.1166/jbn.2019.2866
- ISSN
- 1550-7033
- Abstract
- Ischemic strokes are caused by decreased blood flow into the brain, due to narrowed cerebral arteries. In the ischemic brain, high-mobility group box 1 (HMGB1) is released into extracellular spaces and induces inflammatory reactions. In this study, HMGB1 small interfering RNA (siRNA) was delivered into ischemic brains by intravenous administration using rabies virus glycoprotein (RVG) peptide-decorated exosomes. A fusion protein of RVG and Lamp2b was expressed in 293T cells. Since Lamp2b is an exosome membrane-integral protein, RVG-Lamp2b is integrated into the exosomes, producing RVG-decorated exosomes (RVG-Exo). HMGB1-siRNA was loaded into RVG-Exo and unmodified exosomes (Unmod-Exo) by electroporation. The exosomes were homogenous with a size of less than 50 nm and a negative surface charge. In vitro delivery assays showed that RVG-Exo showed higher efficiency to Neuro2A cells than Unmod-Exo. Also, HMGB1 levels were reduced more effectively by RVG-Exo/HMGB1-siRNA. In vivo delivery efficiency and therapeutic effects of RVG-Exo/HMGB1-siRNA were evaluated in a middle cerebral artery occlusion (MCAO) model. RVG-Exo/HMGB1-siRNA, Unmod-Exo/HMGB1-siRNA, and PEI25k/HMGB1-siRNA were administrated into the MCAO model intravenously through the tail vein. The results showed that HMGB1, tumor necrosis factor-alpha (TNF-alpha), and apoptosis levels in the brain were reduced in the RVG-Exo/HMGB1-siRNA group more efficiently than the other groups. In addition, the infarct size was decreased in the RVG-Exo/HMGB1 group more effectively than the other groups. These results suggest that RVG-Exo with HMGB1-siRNA may have potential as a therapeutic system for the treatment of ischemic strokes.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 공과대학 > 서울 생명공학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4480)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.