Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery

Yeon Lim Jang; Sook Hee Ku; So Jin Lee; Jae Hyung Park; Won Jong Kim; Ick Chan Kwon; Sun Hwa Kim; Ji Hoon Jeong

doi:10.1166/jnn.2014.9583

Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery

Yeon Lim Jang, Sook Hee Ku, So Jin Lee, Jae Hyung Park, Won Jong Kim, Ick Chan Kwon, Sun Hwa Kim, Ji Hoon Jeong

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

25 Citations (Scopus)

Abstract

The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression.

Original language	English
Pages (from-to)	7388-7394
Number of pages	7
Journal	Journal of Nanoscience and Nanotechnology
Volume	14
Issue number	10
DOIs	https://doi.org/10.1166/jnn.2014.9583
Publication status	Published - 2014 Oct 1

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Publisher Copyright:
Copyright © 2014 American Scientific Publishers All rights reserved.

Keywords

Hyaluronic acid
Reducible polyethylenimine
Tumor targeting
siRNA delivery

ASJC Scopus subject areas

Bioengineering
General Chemistry
Biomedical Engineering
General Materials Science
Condensed Matter Physics

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10.1166/jnn.2014.9583

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title = "Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery",

abstract = "The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression.",

keywords = "Hyaluronic acid, Reducible polyethylenimine, Tumor targeting, siRNA delivery",

author = "Jang, {Yeon Lim} and Ku, {Sook Hee} and Lee, {So Jin} and Park, {Jae Hyung} and Kim, {Won Jong} and Kwon, {Ick Chan} and Kim, {Sun Hwa} and Jeong, {Ji Hoon}",

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AU - Jang, Yeon Lim

AU - Ku, Sook Hee

AU - Lee, So Jin

AU - Park, Jae Hyung

AU - Kim, Won Jong

AU - Kwon, Ick Chan

AU - Kim, Sun Hwa

AU - Jeong, Ji Hoon

PY - 2014/10/1

Y1 - 2014/10/1

N2 - The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression.

AB - The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression.

KW - Hyaluronic acid

KW - Reducible polyethylenimine

KW - Tumor targeting

KW - siRNA delivery

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DO - 10.1166/jnn.2014.9583

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ER -

Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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