Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life

Arihiro Kano, Takeshi Yamano, Won Choi Sun, Atsushi Maruyama

Research output: Chapter in Book/Report/Conference proceedingConference contribution

3 Citations (Scopus)

Abstract

Small interfering RNA (siRNA) holds potential as a therapeutic approach to silence targeted gene of disease, but siRNA has limited stability in vivo. Therefore, delivery system of siRNA is the key to siRNA therapeutic application. We attempted to develop a delivery system, which enables siRNA to demonstrate high stability and long blood circulation. We synthesized a series of bottlebrush-type copolymers (BBCs) possessing polycationic backbone (less than 30 wt%) and abundant water-soluble side chains (more than 70 wt%) as siRNA carrier. A siRNA complexed with the BBC was resistant to nuclease and stable in plasma. Especially, the BBC (10 wt% PLL and 90 wt% PEG) having higher grafting ratio (≈ 90 wt%) of water-soluble side chains showed 100-times enhanced stability of siRNA in mouse bloodstream in vivo. Surprisingly, even when the BBC and siRNA separately injected into mouse at 20 min interval, the BBC increased blood half life of the siRNA. These results suggest that the BBC has higher selectivity in its ionic interaction to siRNA than other anionic substance in blood components. To our knowledge, this is the first report of siRNA delivery carrier which prolonged blood circulation of siRNA without resource-consuming preparation process.

Original languageEnglish
Title of host publicationMulti-functional Materials and Structures - International Conference on Multifunctional Materials and Structures
PublisherTrans Tech Publications Ltd
Pages762-764
Number of pages3
ISBN (Print)0878493786, 9780878493784
Publication statusPublished - Jan 1 2008
EventMulti-functional Materials and Structures - International Conference on Multifunctional Materials and Structures - Hong Kong, P.R., China
Duration: Jul 28 2008Jul 31 2008

Publication series

NameAdvanced Materials Research
Volume47-50 PART 1
ISSN (Print)1022-6680

Other

OtherMulti-functional Materials and Structures - International Conference on Multifunctional Materials and Structures
CountryChina
CityHong Kong, P.R.
Period7/28/087/31/08

Fingerprint

Brushes
RNA
Blood
Polymers
Copolymers
Hemodynamics
Phase locked loops
Polyethylene glycols
Water
Genes

All Science Journal Classification (ASJC) codes

  • Engineering(all)

Cite this

Kano, A., Yamano, T., Sun, W. C., & Maruyama, A. (2008). Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life. In Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures (pp. 762-764). (Advanced Materials Research; Vol. 47-50 PART 1). Trans Tech Publications Ltd.

Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life. / Kano, Arihiro; Yamano, Takeshi; Sun, Won Choi; Maruyama, Atsushi.

Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures. Trans Tech Publications Ltd, 2008. p. 762-764 (Advanced Materials Research; Vol. 47-50 PART 1).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Kano, A, Yamano, T, Sun, WC & Maruyama, A 2008, Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life. in Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures. Advanced Materials Research, vol. 47-50 PART 1, Trans Tech Publications Ltd, pp. 762-764, Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures, Hong Kong, P.R., China, 7/28/08.
Kano A, Yamano T, Sun WC, Maruyama A. Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life. In Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures. Trans Tech Publications Ltd. 2008. p. 762-764. (Advanced Materials Research).
Kano, Arihiro ; Yamano, Takeshi ; Sun, Won Choi ; Maruyama, Atsushi. / Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life. Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures. Trans Tech Publications Ltd, 2008. pp. 762-764 (Advanced Materials Research).
@inproceedings{b0b258b1818b4c2795195aa176384505,
title = "Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life",
abstract = "Small interfering RNA (siRNA) holds potential as a therapeutic approach to silence targeted gene of disease, but siRNA has limited stability in vivo. Therefore, delivery system of siRNA is the key to siRNA therapeutic application. We attempted to develop a delivery system, which enables siRNA to demonstrate high stability and long blood circulation. We synthesized a series of bottlebrush-type copolymers (BBCs) possessing polycationic backbone (less than 30 wt{\%}) and abundant water-soluble side chains (more than 70 wt{\%}) as siRNA carrier. A siRNA complexed with the BBC was resistant to nuclease and stable in plasma. Especially, the BBC (10 wt{\%} PLL and 90 wt{\%} PEG) having higher grafting ratio (≈ 90 wt{\%}) of water-soluble side chains showed 100-times enhanced stability of siRNA in mouse bloodstream in vivo. Surprisingly, even when the BBC and siRNA separately injected into mouse at 20 min interval, the BBC increased blood half life of the siRNA. These results suggest that the BBC has higher selectivity in its ionic interaction to siRNA than other anionic substance in blood components. To our knowledge, this is the first report of siRNA delivery carrier which prolonged blood circulation of siRNA without resource-consuming preparation process.",
author = "Arihiro Kano and Takeshi Yamano and Sun, {Won Choi} and Atsushi Maruyama",
year = "2008",
month = "1",
day = "1",
language = "English",
isbn = "0878493786",
series = "Advanced Materials Research",
publisher = "Trans Tech Publications Ltd",
pages = "762--764",
booktitle = "Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures",

}

TY - GEN

T1 - Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life

AU - Kano, Arihiro

AU - Yamano, Takeshi

AU - Sun, Won Choi

AU - Maruyama, Atsushi

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Small interfering RNA (siRNA) holds potential as a therapeutic approach to silence targeted gene of disease, but siRNA has limited stability in vivo. Therefore, delivery system of siRNA is the key to siRNA therapeutic application. We attempted to develop a delivery system, which enables siRNA to demonstrate high stability and long blood circulation. We synthesized a series of bottlebrush-type copolymers (BBCs) possessing polycationic backbone (less than 30 wt%) and abundant water-soluble side chains (more than 70 wt%) as siRNA carrier. A siRNA complexed with the BBC was resistant to nuclease and stable in plasma. Especially, the BBC (10 wt% PLL and 90 wt% PEG) having higher grafting ratio (≈ 90 wt%) of water-soluble side chains showed 100-times enhanced stability of siRNA in mouse bloodstream in vivo. Surprisingly, even when the BBC and siRNA separately injected into mouse at 20 min interval, the BBC increased blood half life of the siRNA. These results suggest that the BBC has higher selectivity in its ionic interaction to siRNA than other anionic substance in blood components. To our knowledge, this is the first report of siRNA delivery carrier which prolonged blood circulation of siRNA without resource-consuming preparation process.

AB - Small interfering RNA (siRNA) holds potential as a therapeutic approach to silence targeted gene of disease, but siRNA has limited stability in vivo. Therefore, delivery system of siRNA is the key to siRNA therapeutic application. We attempted to develop a delivery system, which enables siRNA to demonstrate high stability and long blood circulation. We synthesized a series of bottlebrush-type copolymers (BBCs) possessing polycationic backbone (less than 30 wt%) and abundant water-soluble side chains (more than 70 wt%) as siRNA carrier. A siRNA complexed with the BBC was resistant to nuclease and stable in plasma. Especially, the BBC (10 wt% PLL and 90 wt% PEG) having higher grafting ratio (≈ 90 wt%) of water-soluble side chains showed 100-times enhanced stability of siRNA in mouse bloodstream in vivo. Surprisingly, even when the BBC and siRNA separately injected into mouse at 20 min interval, the BBC increased blood half life of the siRNA. These results suggest that the BBC has higher selectivity in its ionic interaction to siRNA than other anionic substance in blood components. To our knowledge, this is the first report of siRNA delivery carrier which prolonged blood circulation of siRNA without resource-consuming preparation process.

UR - http://www.scopus.com/inward/record.url?scp=56349163696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=56349163696&partnerID=8YFLogxK

M3 - Conference contribution

AN - SCOPUS:56349163696

SN - 0878493786

SN - 9780878493784

T3 - Advanced Materials Research

SP - 762

EP - 764

BT - Multi-functional Materials and Structures - International Conference on Multifunctional Materials and Structures

PB - Trans Tech Publications Ltd

ER -