pH-responsive oligodeoxynucleotide (ODN)-poly(ethylene glycol) conjugate through acid-labile β-thiopropionate linkage: Preparation and polyion complex micelle formation

Motoi Oishi, Shigeki Sasaki, Yukio Nagasaki, Kazunori Kataoka

研究成果: ジャーナルへの寄稿学術誌査読

143 被引用数 (Scopus)

抄録

An oligodeoxynucleotide (ODN) conjugated to poly(ethylene glycol) (PEG) through a pH-responsive ester linkage (PEG-ODN conjugate) was successfully synthesized by the Michael reaction of 3′-thiol-modified ODN with a heterobifunctional PEG bearing an acetal group at the α-end and an acrylate group at the ω-end (acetal-PEG-acrylate), aimed at the development of a novel ODN delivery system. The prepared PEG-ODN conjugate and linear-poy(ethyleneimine) (L-PEI) spontaneously associated to form a polyion complex (PIC) micelle whose diameter and polydispersity index (μ22) were 102.5 nm and 0.096 as determined by DLS measurements, respectively. Both the PEG-ODN conjugate and PIC micelle showed cleavage of the ester linkage at the endosomal pH (=5.5), suggesting that the PIC micelle is anticipated to release the ODN in the intracellular compartment. Furthermore, the PEG-ODN conjugate in the PIC micelle was stable against deoxyribonuclase (DNase I) digestion and has no interaction with the serum component because of the steric stabilization of the highly dense PEG corona surrounding the PIC core. These characteristics of the PIC micelles entrapping the PEG-ODN conjugate are promising for their utility as a novel ODN delivery system.

本文言語英語
ページ(範囲)1426-1432
ページ数7
ジャーナルBiomacromolecules
4
5
DOI
出版ステータス出版済み - 9月 2003

!!!All Science Journal Classification (ASJC) codes

  • バイオエンジニアリング
  • 生体材料
  • ポリマーおよびプラスチック
  • 材料化学

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