Abstract
This study aims to develop bioreducible polyethylenimine (rPEI)/siRNA polyplexes with high stability, high transfection efficiency, and low cytotoxicity for efficient cytoplasmic siRNA delivery. rPEI successfully incorporated siRNA into stable and compact nanocomplexes, and the disulfide linkages in rPEI/siRNA were cleaved under reductive environments, resulting in efficient intracellular translocation and siRNA release. In this study, receptor for advanced glycation end-products (RAGE) was selected as a therapeutic target gene because it is associated with inflammatory responses in ischemia/reperfusion injury. rPEI/siRAGE exhibited high target gene silencing and low cytotoxicity in cardiomyocytes, and the treatment of rPEI/siRAGE reduced the myocardial infarction size. Bioreducible polyethylenimine (rPEI) is synthesized from low molecular weight PEI via cleavable disulfide linkages to achieve high stability, high transfection efficiency, high cytoplasmic siRNA release, and low cytotoxicity. rPEI/siRAGE polyplex can reduce RAGE expression in ischemic/reperfused myocardium, thereby leading to attenuation of myocardial infarction.
| Original language | English |
|---|---|
| Pages (from-to) | 1755-1763 |
| Number of pages | 9 |
| Journal | Macromolecular Bioscience |
| Volume | 15 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2015 Dec 1 |
| Externally published | Yes |
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Keywords
- bioreducible polyethylenimine
- cytoplasmic delivery
- myocardial infarction
- RAGE
- siRNA
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biomaterials
- Polymers and Plastics
- Materials Chemistry
Cite this
Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy. / Yang, Min Jung; Ku, Sook Hee; Kim, Dongkyu; Kim, Won Jong; Mok, Hyejung; Kim, Sun Hwa; Kwon, Ick Chan.
In: Macromolecular Bioscience, Vol. 15, No. 12, 01.12.2015, p. 1755-1763.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy
AU - Yang, Min Jung
AU - Ku, Sook Hee
AU - Kim, Dongkyu
AU - Kim, Won Jong
AU - Mok, Hyejung
AU - Kim, Sun Hwa
AU - Kwon, Ick Chan
PY - 2015/12/1
Y1 - 2015/12/1
N2 - This study aims to develop bioreducible polyethylenimine (rPEI)/siRNA polyplexes with high stability, high transfection efficiency, and low cytotoxicity for efficient cytoplasmic siRNA delivery. rPEI successfully incorporated siRNA into stable and compact nanocomplexes, and the disulfide linkages in rPEI/siRNA were cleaved under reductive environments, resulting in efficient intracellular translocation and siRNA release. In this study, receptor for advanced glycation end-products (RAGE) was selected as a therapeutic target gene because it is associated with inflammatory responses in ischemia/reperfusion injury. rPEI/siRAGE exhibited high target gene silencing and low cytotoxicity in cardiomyocytes, and the treatment of rPEI/siRAGE reduced the myocardial infarction size. Bioreducible polyethylenimine (rPEI) is synthesized from low molecular weight PEI via cleavable disulfide linkages to achieve high stability, high transfection efficiency, high cytoplasmic siRNA release, and low cytotoxicity. rPEI/siRAGE polyplex can reduce RAGE expression in ischemic/reperfused myocardium, thereby leading to attenuation of myocardial infarction.
AB - This study aims to develop bioreducible polyethylenimine (rPEI)/siRNA polyplexes with high stability, high transfection efficiency, and low cytotoxicity for efficient cytoplasmic siRNA delivery. rPEI successfully incorporated siRNA into stable and compact nanocomplexes, and the disulfide linkages in rPEI/siRNA were cleaved under reductive environments, resulting in efficient intracellular translocation and siRNA release. In this study, receptor for advanced glycation end-products (RAGE) was selected as a therapeutic target gene because it is associated with inflammatory responses in ischemia/reperfusion injury. rPEI/siRAGE exhibited high target gene silencing and low cytotoxicity in cardiomyocytes, and the treatment of rPEI/siRAGE reduced the myocardial infarction size. Bioreducible polyethylenimine (rPEI) is synthesized from low molecular weight PEI via cleavable disulfide linkages to achieve high stability, high transfection efficiency, high cytoplasmic siRNA release, and low cytotoxicity. rPEI/siRAGE polyplex can reduce RAGE expression in ischemic/reperfused myocardium, thereby leading to attenuation of myocardial infarction.
KW - bioreducible polyethylenimine
KW - cytoplasmic delivery
KW - myocardial infarction
KW - RAGE
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=84955177488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955177488&partnerID=8YFLogxK
U2 - 10.1002/mabi.201500213
DO - 10.1002/mabi.201500213
M3 - Article
C2 - 26287505
AN - SCOPUS:84955177488
VL - 15
SP - 1755
EP - 1763
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
SN - 1616-5187
IS - 12
ER -