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 journalArticlepeer-review

92 Citations (Scopus)

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

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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