Journal
BIOMATERIALS
Volume 146, Issue -, Pages 136-145Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.09.014
Keywords
Injectable hydrogel; Photothermal immunotherapy; CpG motif; Laser responsive immunoadjuvant; DNA nanotechnology
Funding
- Japan Society for the Promotion of Science (JSPS) [23390010, 26293008]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [25114706]
- JST CREST [JPMJCR1521]
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [17H03047, 25114706] Funding Source: KAKEN
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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-gamma production from splenocytes. Moreover, the treatment significantly retarded the tumor growth and extended the survival of the tumor-bearing mice. (C) 2017 Elsevier Ltd. All rights reserved.
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