PEG-appended β-(1→3)-D-glucan schizophyllan to deliver antisense-oligonucleotides with avoiding lysosomal degradation

Ryouji Karinaga, Kazuya Koumoto, Masami Mizu, Takahisa Anada, Seiji Shinkai, Kazuo Sakurai

研究成果: Contribution to journalArticle査読

20 被引用数 (Scopus)

抄録

Schizophyllan is a natural β-(1→3)-d-glucan existing as a triple helix in water and as a single chain in dimethylsulfoxide (DMSO). As we already reported, when a homo-polynucleotide [e.g., poly(dA) or poly(C)] is added to the schizophyllan/DMSO solution and subsequently DMSO is exchanged for water, the single chain of schizophyllan forms a complex with the polynucleotide. One of the potential applications for this novel complex is an antisense- oligonucleotide (AS ODN) carrier. The present paper describes a modification technique that enabled us to introduce PEG only to the side chain of schizophyllan. This technique consisted of periodate oxidation of the glucose side chain and subsequent reaction between methoxypolyethylene glycol amine and the formyl terminate, followed by reduction with NaBH4. Subsequently, we made a complex from PEG-appended schizophyllan and an AS ODN sequence, and carried out an in vitro antisense assay, administrating the AS ODN complex to depress A375 c-myb mRNA of A375 melanoma cell lines. The PEG-SPG/AS ODN complex showed more enhanced antisnese effect than naked AS ODN dose, i.e., the same level as that of RGD-appended SPG. Here, the RGD system has been shown one on the most effective AS ODN carrier (Science 261 (1993) 1004-1012). When we added nigericin to the assay system, the antisense effect was not affected in the PEG-SPG system, on the other hand, it was almost eliminated in the RGD system. Nigericin is well known to interrupt transport from endosome to lysosome. Therefore, the difference between the PEG and RGD complexes indicates that, in the PEG system, AS ODN was able to escape from lysosomal degradation. The present work has thus proposed a new strategy to delivery AS ODN using schizophyllan as a new carrier.

本文言語英語
ページ(範囲)4866-4873
ページ数8
ジャーナルBiomaterials
26
23
DOI
出版ステータス出版済み - 8 2005

All Science Journal Classification (ASJC) codes

  • バイオエンジニアリング
  • セラミックおよび複合材料
  • 生物理学
  • 生体材料
  • 材料力学

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