Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy.
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.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea.|KU-KIST Graduate School, Korea University, Seoul, 136-701, Republic of Korea.
Min Jung
MJ
Yang
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea.
Sook Hee
SH
Ku
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea.|Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, 120-752, Republic of Korea.
Dongkyu
D
Kim
Department of Chemistry, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
Won Jong
WJ
Kim
Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Republic of Korea.
Hyejung
H
Mok
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea. sunkim@kist.re.kr.
Sun Hwa
SH
Kim
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea. ikwon@kist.re.kr.|KU-KIST Graduate School, Korea University, Seoul, 136-701, Republic of Korea. ikwon@kist.re.kr.
Ick Chan
IC
Kwon
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D053758:Nanoparticles; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
C000593874:Ager protein, rat; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products
RAGE; bioreducible polyethylenimine; cytoplasmic delivery; myocardial infarction; siRNA