Injectable, self-gelling, biodegradable, and immunomodulatory DNA hydrogel for antigen delivery

JOURNAL OF CONTROLLED RELEASE

卷:180

Article

Nishikawa, Makiya¹  Ogawa, Kohei¹  Umeki, Yuka¹  Mohri, Kohta¹  Kawasaki, Yohji²  Watanabe, Hiroshi²  Takahashi, Natsuki¹  Kusuki, Eri¹  Takahashi, Rei³  Takahashi, Yuki¹  Takakura, Yoshinobu¹ 

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut & Drug Metab, Sakyo Ku, Kyoto 6068501, Japan

[2] Kyoto Univ, Inst Chem Res, Uji, Kyoto 6110011, Japan

[3] Doshisha Womens Coll Liberal Arts, Fac Pharmaceut Sci, Dept Pharmacotherapeut, Kyoto 6100395, Japan

关键词: Hydrogel;    CpG motif;    Controlled release;    Antigen;    Immune cell;    Self-gelling;   

DOI  :  10.1016/j.jconrel.2014.02.001

来源: Elsevier

【 摘 要 】

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 0.25 s. 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. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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