DNA nanotechnology-based composite-type gold nanoparticle-immunostimulatory DNA hydrogel for tumor photothermal immunotherapy. (November 2017)

• Record Type: Journal Article
• Authors: Yata, Tomoya; Takahashi, Yuki; Tan, Mengmeng; Nakatsuji, Hirotaka; Ohtsuki, Shozo; Murakami, Tatsuya; Imahori, Hiroshi; Umeki, Yuka; Shiomi, Tomoki; Takakura, Yoshinobu; Nishikawa, Makiya
• Is Part Of: Biomaterials. Volume 146(2017)
• Page Start: 136
• Page End: 145
• Publication Date: 2017-11
• Subjects: Injectable hydrogel -- Photothermal immunotherapy -- CpG motif -- Laser responsive immunoadjuvant -- DNA nanotechnology; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2017.09.014
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Success of tumor photothermal immunotherapy requires a system that induces heat stress in cancer cells and enhances strong anti-tumor immune responses. Here, we designed a composite-type immunostimulatory DNA hydrogel consisting of a hexapod-like structured DNA (hexapodna) with CpG sequences and gold nanoparticles. Mixing of the properly designed hexapodna and oligodeoxynucleotide-modified gold nanoparticles resulted in the formation of composite-type gold nanoparticle-DNA hydrogels. Laser irradiation of the hydrogel resulted in the release of hexapodna, which efficiently stimulated immune cells to release proinflammatory cytokines. Then, EG7-OVA tumor-bearing mice received an intratumoral injection of a gold nanoparticle-DNA hydrogel, followed by laser irradiation at 780 nm. This treatment increased the local temperature and the mRNA expression of heat shock protein 70 in the tumor tissue, increased tumor-associated antigen-specific IgG levels in the serum, and induced tumor-associated antigen-specific interferon-γ production from splenocytes. Moreover, the treatment significantly retarded the tumor growth and extended the survival of the tumor-bearing mice. Graphical abstract: Highlights: Hydrogel has hexapod-like structured DNA and gold nanoparticles with CpG sequences. The hydrogel was photothermally active and released highly ordered DNAs. Intratumoral hydrogel injection and laser irradiation inhibited tumor growth.