PEG conjugated VEGF siRNA for anti-angiogenic gene therapy

Sun Hwa Kim; Ji Hoon Jeong; Soo Hyun Lee; Sung Wan Kim; Tae Gwan Park

doi:10.1016/j.jconrel.2006.05.023

PEG conjugated VEGF siRNA for anti-angiogenic gene therapy

Sun Hwa Kim, Ji Hoon Jeong, Soo Hyun Lee, Sung Wan Kim, Tae Gwan Park

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

256 Scopus citations

Abstract

A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.

Original language	English
Pages (from-to)	123-129
Number of pages	7
Journal	Journal of Controlled Release
Volume	116
Issue number	2 SPEC. ISS.
DOIs	https://doi.org/10.1016/j.jconrel.2006.05.023
State	Published - Nov 28 2006
Externally published	Yes

Funding

This work was supported by the grants from the Ministry of Science and Technology (M10414030002-05N1403-00210), Korea and from the National Institute of Health (CA107070), USA.

Funders	Funder number
National Institute of Health
National Cancer Institute	R01CA107070
Ministerio de Ciencia y Tecnología	M10414030002-05N1403-00210

Keywords

Gene delivery
Polyelectrolyte complex micelles
Vascular endothelial growth factor
siRNA-PEG conjugate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jconrel.2006.05.023

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title = "PEG conjugated VEGF siRNA for anti-angiogenic gene therapy",

abstract = "A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.",

keywords = "Gene delivery, Polyelectrolyte complex micelles, Vascular endothelial growth factor, siRNA-PEG conjugate",

author = "Kim, {Sun Hwa} and Jeong, {Ji Hoon} and Lee, {Soo Hyun} and Kim, {Sung Wan} and Park, {Tae Gwan}",

year = "2006",

month = nov,

day = "28",

doi = "10.1016/j.jconrel.2006.05.023",

language = "English",

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T1 - PEG conjugated VEGF siRNA for anti-angiogenic gene therapy

AU - Kim, Sun Hwa

AU - Jeong, Ji Hoon

AU - Lee, Soo Hyun

AU - Kim, Sung Wan

AU - Park, Tae Gwan

PY - 2006/11/28

Y1 - 2006/11/28

N2 - A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.

AB - A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.

KW - Gene delivery

KW - Polyelectrolyte complex micelles

KW - Vascular endothelial growth factor

KW - siRNA-PEG conjugate

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U2 - 10.1016/j.jconrel.2006.05.023

DO - 10.1016/j.jconrel.2006.05.023

M3 - Article

C2 - 16831481

AN - SCOPUS:33845216721

SN - 0168-3659

VL - 116

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EP - 129

JO - Journal of Controlled Release

JF - Journal of Controlled Release

IS - 2 SPEC. ISS.

ER -

PEG conjugated VEGF siRNA for anti-angiogenic gene therapy

Abstract

Funding

Keywords

UN SDGs

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