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

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1426-1432
Number of pages7
JournalBiomacromolecules
Volume4
Issue number5
DOIs
Publication statusPublished - Sep 1 2003

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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