Ternary complex consisting of DNA, polycation, and a natural polysaccharide of schizophyllan to induce cellular uptake by antigen presenting cells

Yoichi Takeda, Naohiko Shimada, Kenji Kaneko, Seiji Shinkai, Kazuo Sakurai

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A natural polysaccharide called schizophyllan (SPG) can form a complex with polynucleotides, and the complex has been shown to deliver biofunctional short DNAs such as antisense DNAs and CpG-DNAs. Although it is a novel and efficient method, there is a drawback: attachment of homo-polynucleotide tails [for example, poly-(dA) or poly(C)] to the end of DNA is necessary to stabilize the complex, because DNA heterosequences cannot bind to SPG. The aim of this paper is to present an alternative method in which SPG/DNA complexes can be made without using the tails. The basic strategy is as follows: since SPG can form hydrophobic domains in aqueous solutions, hydrophobic objects should be encapsulated by this domain. DNA alone is highly hydrophilic; however, once DNA/polycation complexes are made, they should be included by the SPG hydrophobic domain. The aim of this paper is to prove the formation of the polycation/DNA/SPG ternary complex. Gel electrophoresis showed that presence of SPG influenced the migration pattern of polycation+DNA mixtures. With increasing the SPG ratio, the zeta potential (ζ) of the polycation+DNA+SPG mixture decreased drastically to reach almost ζ = 0 and the particle size distributions were altered due to the ternary complex formation. Confocal laser scanning microscopy revealed that the polycation/DNA/SPG ternary complexes showed high uptake efficiency when the complexes were exposed to macrophage-like cells (J774.A1). IL-12 secretion was enhanced when CpG-DNA was added as the ternary complex. These features can be ascribed to the fact that J774.A1 has a SPG recognition site called Dectin-1 on the cellular surface and the ternary complex can be ingested by this pathway.

Original languageEnglish
Pages (from-to)1178-1186
Number of pages9
JournalBiomacromolecules
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 1 2007

Fingerprint

Sizofiran
Polysaccharides
DNA
Polynucleotides
Antigen-Presenting Cells
polycations
Antisense DNA
Poly C
Macrophages
Zeta potential
Interleukin-12
Electrophoresis

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Ternary complex consisting of DNA, polycation, and a natural polysaccharide of schizophyllan to induce cellular uptake by antigen presenting cells. / Takeda, Yoichi; Shimada, Naohiko; Kaneko, Kenji; Shinkai, Seiji; Sakurai, Kazuo.

In: Biomacromolecules, Vol. 8, No. 4, 01.04.2007, p. 1178-1186.

Research output: Contribution to journalArticle

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