Supramolecular assemblies for the cytoplasmic delivery of antisense oligodeoxynucleotide: Polyion complex (PIC) micelles based on poly(ethylene glycol)-SS-oligodeoxynucleotide conjugate

Motoi Oishi, Tetsuya Hayama, Yoshitsugu Akiyama, Seiji Takae, Atsushi Harada, Yuichi Yamasaki, Fumi Nagatsugi, Shigeki Sasaki, Yukio Nagasaki, Kazunori Kataoka

Research output: Contribution to journalArticle

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Abstract

A novel cytoplasmic delivery system of antisense oligodeoxynucleotide (asODN) was developed by assembling a PEG-asODN conjugate with disulfide linkage (smart linkage) (PEG-SS-asODN) into polyion complex (PIC) micelles through the complexation with branched poly(ethylenimine) (B-PEI). The PIC micelle thus prepared showed a significant antisense effect against luciferase gene expression in HuH-7 cells, far more efficient than nonmicelle systems (asODN and PEG-SS-asODN in free form) and PIC micelle encapsulating the conjugate without the disulfide linkage. Use of poly(l-lysine) (PLL) instead of the B-PEI for PIC micellization led to a substantial decrease in the antisense effect. These results indicate that the PIC micelles formulated from PEG-SS-asODN conjugate and B-PEI is successfully transported from the endosomal compartment into the cytoplasm by the buffering effect of the B-PEI, releasing hundreds of active asODN molecules via cleavage of the disulfide linkage into the cellular interior, responding to a high glutathione concentration in the cytoplasmic compartment. Furthermore, the type of smart linkage (glutathione-sensitive SS linkage vs pH-sensitive linkage) in the conjugates substantially affected the antisense effect of the PIC micelles, depending on the nature of the counter polycation (B-PEI vs PLL.

Original languageEnglish
Pages (from-to)2449-2454
Number of pages6
JournalBiomacromolecules
Volume6
Issue number5
DOIs
Publication statusPublished - Sep 1 2005

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Ethylene Glycol
Oligodeoxyribonucleotides
Micelles
Polyethylene glycols
Polyetherimides
Disulfides
Phase locked loops
Glutathione
Micellization
Complexation
Luciferases
Gene expression
Lysine
Cytoplasm
Gene Expression
Molecules
polyethylene glycol bis(succinimidyl succinate)

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Supramolecular assemblies for the cytoplasmic delivery of antisense oligodeoxynucleotide : Polyion complex (PIC) micelles based on poly(ethylene glycol)-SS-oligodeoxynucleotide conjugate. / Oishi, Motoi; Hayama, Tetsuya; Akiyama, Yoshitsugu; Takae, Seiji; Harada, Atsushi; Yamasaki, Yuichi; Nagatsugi, Fumi; Sasaki, Shigeki; Nagasaki, Yukio; Kataoka, Kazunori.

In: Biomacromolecules, Vol. 6, No. 5, 01.09.2005, p. 2449-2454.

Research output: Contribution to journalArticle

Oishi, Motoi ; Hayama, Tetsuya ; Akiyama, Yoshitsugu ; Takae, Seiji ; Harada, Atsushi ; Yamasaki, Yuichi ; Nagatsugi, Fumi ; Sasaki, Shigeki ; Nagasaki, Yukio ; Kataoka, Kazunori. / Supramolecular assemblies for the cytoplasmic delivery of antisense oligodeoxynucleotide : Polyion complex (PIC) micelles based on poly(ethylene glycol)-SS-oligodeoxynucleotide conjugate. In: Biomacromolecules. 2005 ; Vol. 6, No. 5. pp. 2449-2454.
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abstract = "A novel cytoplasmic delivery system of antisense oligodeoxynucleotide (asODN) was developed by assembling a PEG-asODN conjugate with disulfide linkage (smart linkage) (PEG-SS-asODN) into polyion complex (PIC) micelles through the complexation with branched poly(ethylenimine) (B-PEI). The PIC micelle thus prepared showed a significant antisense effect against luciferase gene expression in HuH-7 cells, far more efficient than nonmicelle systems (asODN and PEG-SS-asODN in free form) and PIC micelle encapsulating the conjugate without the disulfide linkage. Use of poly(l-lysine) (PLL) instead of the B-PEI for PIC micellization led to a substantial decrease in the antisense effect. These results indicate that the PIC micelles formulated from PEG-SS-asODN conjugate and B-PEI is successfully transported from the endosomal compartment into the cytoplasm by the buffering effect of the B-PEI, releasing hundreds of active asODN molecules via cleavage of the disulfide linkage into the cellular interior, responding to a high glutathione concentration in the cytoplasmic compartment. Furthermore, the type of smart linkage (glutathione-sensitive SS linkage vs pH-sensitive linkage) in the conjugates substantially affected the antisense effect of the PIC micelles, depending on the nature of the counter polycation (B-PEI vs PLL.",
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