氧化应激
干扰素基因刺激剂
DNA损伤
免疫系统
活性氧
免疫原性
肿瘤微环境
癌症研究
细胞生物学
免疫原性细胞死亡
谷胱甘肽
生物
免疫疗法
免疫学
先天免疫系统
DNA
生物化学
酶
作者
Shengjie Sun,Mian Yu,Yu Liu,Weijian Huang,Ming Zhu,Yanan Fu,Lingchen Yan,Qiang Wang,Xiaoyuan Ji,Jing Zhao,Meiying Wu
出处
期刊:Biomaterials
[Elsevier]
日期:2023-05-01
卷期号:296: 122068-122068
被引量:6
标识
DOI:10.1016/j.biomaterials.2023.122068
摘要
Photodynamic therapy (PDT)-mediated antitumor immune response depends on oxidative stress intensity and subsequent immunogenic cell death (ICD) in tumor cells, yet the inherent antioxidant system restricts reactive oxygen species (ROS)-associated oxidative damage, which is highly correlated with the upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and the downstream products, such as glutathione (GSH). Herein, to overcome this dilemma, we designed a versatile nanoadjuvant (RI@Z-P) to enhance the sensitivity of tumor cells to oxidative stress via Nrf2-specific small interfering RNA (siNrf2). The constructed RI@Z-P could significantly amplify photooxidative stress and achieve robust DNA oxidative damage, activating the stimulator of interferon genes (STING)-dependent immune-sensing to produce interferon-β (IFN-β). Additionally, RI@Z-P together with laser irradiation reinforced tumor immunogenicity by exposing or releasing damage-associated molecular patterns (DAMPs), showing the prominent adjuvant effect for promoting dendritic cell (DC) maturation and T-lymphocyte activation and even alleviating the immunosuppressive microenvironment to some extent.
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