Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery

Makoto Oba, Kanjiro Miyata, Kensuke Osada, R. James Christie, Mai Sanjoh, Weidong Li, Shigeto Fukushima, Takehiko Ishii, Mitsunobu Kano, Nobuhiro Nishiyama, Hiroyuki Koyama, Kazunori Kataoka

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Polyplex micelles formed with plasmid DNA (pDNA) and poly(ethylene glycol) (PEG)-block-poly{ N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] exhibit effective endosomal escaping properties based on di-protonation of diamine side chains with decreasing pH, which improves their transfection efficiency and thus are promising candidates for local in vivo gene transfer. Here, PEG-PAsp(DET) polyplex micelles were further improved as in vivo systemic vectors by introduction of cholesterol (Chole) into the ω-terminus of PEG-PAsp(DET) to obtain PEG-PAsp(DET)-Chole. Introduction of the cholesterol resulted in enhanced association of block copolymers with pDNA, which led to increased stability in proteinous medium and also in the blood stream after systemic injection compared to PEG-PAsp(DET) micelles. The synergistic effect between enhanced polymer association with pDNA and increased micelle stability of PEG-PAsp(DET)-Chole polyplex micelles led to high in vitro gene transfer even at relatively low concentrations, due to efficient cellular uptake and effective endosomal escape of block copolymers and pDNA. Finally, PEG-PAsp(DET)-Chole micelles achieved significant suppression of tumor growth following intravenous injection into mice bearing a subcutaneous pancreatic tumor using therapeutic pDNA encoding an anti-angiogenic protein. These results suggest that PEG-PAsp(DET)-Chole micelles can be effective systemic gene vectors for treatment of solid tumors.

Original languageEnglish
Pages (from-to)652-663
Number of pages12
JournalBiomaterials
Volume32
Issue number2
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Fingerprint

Ethylene Glycol
Micelles
Polyethylene glycols
Block copolymers
Cholesterol
Genes
Plasmids
DNA
Gene transfer
Tumors
Bearings (structural)
Angiogenic Proteins
Association reactions
Neoplasms
Diamines
polycations
PAsp(DET)
Protonation
Intravenous Injections
Transfection

Keywords

  • Anti-angiogenic therapy
  • Cholesterol
  • Non-viral gene vector
  • Pancreatic tumor
  • Polyplex micelle

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Oba, M., Miyata, K., Osada, K., Christie, R. J., Sanjoh, M., Li, W., ... Kataoka, K. (2011). Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery. Biomaterials, 32(2), 652-663. https://doi.org/10.1016/j.biomaterials.2010.09.022

Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery. / Oba, Makoto; Miyata, Kanjiro; Osada, Kensuke; Christie, R. James; Sanjoh, Mai; Li, Weidong; Fukushima, Shigeto; Ishii, Takehiko; Kano, Mitsunobu; Nishiyama, Nobuhiro; Koyama, Hiroyuki; Kataoka, Kazunori.

In: Biomaterials, Vol. 32, No. 2, 01.2011, p. 652-663.

Research output: Contribution to journalArticle

Oba, M, Miyata, K, Osada, K, Christie, RJ, Sanjoh, M, Li, W, Fukushima, S, Ishii, T, Kano, M, Nishiyama, N, Koyama, H & Kataoka, K 2011, 'Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery', Biomaterials, vol. 32, no. 2, pp. 652-663. https://doi.org/10.1016/j.biomaterials.2010.09.022
Oba, Makoto ; Miyata, Kanjiro ; Osada, Kensuke ; Christie, R. James ; Sanjoh, Mai ; Li, Weidong ; Fukushima, Shigeto ; Ishii, Takehiko ; Kano, Mitsunobu ; Nishiyama, Nobuhiro ; Koyama, Hiroyuki ; Kataoka, Kazunori. / Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery. In: Biomaterials. 2011 ; Vol. 32, No. 2. pp. 652-663.
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