Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy

Min Jung Yang; Sook Hee Ku; Dongkyu Kim; Won Jong Kim; Hyejung Mok; Sun Hwa Kim; Ick Chan Kwon

doi:10.1002/mabi.201500213

Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy

Min Jung Yang, Sook Hee Ku, Dongkyu Kim, Won Jong Kim, Hyejung Mok, Sun Hwa Kim, Ick Chan Kwon

KU-KIST Graduate School of Converging Science and Technology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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	https://doi.org/10.1002/mabi.201500213
Publication status	Published - 2015 Dec 1

Keywords

RAGE
bioreducible polyethylenimine
cytoplasmic delivery
myocardial infarction
siRNA

ASJC Scopus subject areas

Biotechnology
Bioengineering
Biomaterials
Polymers and Plastics
Materials Chemistry

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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 › peer-review

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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.",

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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.

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Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine-based Nanocarriers for Myocardial Gene Therapy

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