Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan.
Biomaterials. 2017 Nov;146:136-145. doi: 10.1016/j.biomaterials.2017.09.014. Epub 2017 Sep 9.
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.
肿瘤光热免疫治疗的成功需要一个能够在癌细胞中诱导热应激并增强强烈的抗肿瘤免疫反应的系统。在这里，我们设计了一种由具有 CpG 序列的六足结构 DNA（六足 DNA）和金纳米粒子组成的复合免疫刺激 DNA 水凝胶。适当设计的六足 DNA 与寡脱氧核苷酸修饰的金纳米粒子混合后，形成了复合金纳米粒子-DNA 水凝胶。水凝胶的激光照射导致六足 DNA 的释放，有效地刺激免疫细胞释放促炎细胞因子。然后，EG7-OVA 荷瘤小鼠接受金纳米粒子-DNA 水凝胶的瘤内注射，随后在 780nm 激光下照射。该治疗方法提高了肿瘤组织中局部温度和热休克蛋白 70 的 mRNA 表达水平，增加了血清中肿瘤相关抗原特异性 IgG 水平，并诱导了来自脾细胞的肿瘤相关抗原特异性干扰素-γ产生。此外，该治疗方法显著抑制了肿瘤生长并延长了荷瘤小鼠的生存时间。
