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j.jconrel.2014.02.001.pdf | 691.32 kB | Adobe PDF | 見る/開く |
タイトル: | Injectable, self-gelling, biodegradable, and immunomodulatory DNA hydrogel for antigen delivery. |
著者: | Nishikawa, Makiya Ogawa, Kohei Umeki, Yuka Mohri, Kohta Kawasaki, Yohji Watanabe, Hiroshi https://orcid.org/0000-0003-0826-2454 (unconfirmed) Takahashi, Natsuki Kusuki, Eri Takahashi, Rei Takahashi, Yuki https://orcid.org/0000-0002-8772-2772 (unconfirmed) Takakura, Yoshinobu https://orcid.org/0000-0002-7359-2647 (unconfirmed) |
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 BV |
誌名: | Journal of controlled release |
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. 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。 This is not the published version. Please cite only the published version. |
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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