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タイトル: Injectable, self-gelling, biodegradable, and immunomodulatory DNA hydrogel for antigen delivery.
著者: Nishikawa, Makiya  kyouindb  KAKEN_id
Ogawa, Kohei
Umeki, Yuka
Mohri, Kohta
Kawasaki, Yohji
Watanabe, Hiroshi  kyouindb  KAKEN_id
Takahashi, Natsuki
Kusuki, Eri
Takahashi, Rei
Takahashi, Yuki  kyouindb  KAKEN_id
Takakura, Yoshinobu  kyouindb  KAKEN_id
著者名の別形: 西川, 元也
キーワード: Hydrogel
CpG motif
Controlled release
Antigen
Immune cell
Self-gelling
発行日: 28-Apr-2014
出版者: Elsevier B.V.
誌名: Journal of controlled release : official journal of the Controlled Release Society
巻: 180
開始ページ: 25
終了ページ: 32
抄録: DNA nanotechnology-based nanosystems and macrosystems have attracted much attention in the biomedical research field. The nature of DNA endows these systems with biodegradable, biocompatible, and immunomodulatory properties. Here, we present an injectable hydrogel system that consists only of chemically synthesized short DNA strands, water, and salts. Several preparations of polypod-like structured DNA, or polypodna, were designed, including tri-, tetra-, penta- and hexapodna, as the building blocks of self-gelling DNA hydrogel. Under physiological conditions, properly designed polypodna preparations formed a hydrogel. The analysis of the modulus data of the hydrogel consisting of two sets of hexapodna preparations showed that this injectable hydrogel was reorganized at a time scale of 0.25s. Then, DNA hydrogel containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides was used to stimulate innate immunity through Toll-like receptor 9, the receptor for CpG DNA. Gel formation significantly increased the activity of immunostimulatory CpG DNA, retarded the clearance after intradermal injection into mice, and increased the immune responses to ovalbumin (OVA) incorporated into the hydrogel as a model antigen. OVA/CpG DNA hydrogel induced much less local or systemic adverse reactions than OVA injected with complete Freund's adjuvant or alum. GpC DNA hydrogel containing no CpG sequences was less effective, indicating the importance of immunomodulation by CpG DNA hydrogel. Thus, we have created an efficient system for sustained delivery of antigens or other bioactive compounds.
著作権等: © 2014 Elsevier B.V.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/185154
DOI(出版社版): 10.1016/j.jconrel.2014.02.001
PubMed ID: 24530618
出現コレクション:学術雑誌掲載論文等

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