Details

Autor(en) / Beteiligte

• Sun, Shengjie
• Yu, Mian
• Yu, Liu
• Huang, Wenxin
• Zhu, Meishu
• Fu, Yanan
• Yan, Lingchen
• Wang, Qiang
• Ji, Xiaoyuan
• Zhao, Jing
• Wu, Meiying

Titel

Nrf2 silencing amplifies DNA photooxidative damage to activate the STING pathway for synergistic tumor immunotherapy

Ist Teil von

• Biomaterials, 2023-05, Vol.296, p.122068-122068, Article 122068

Ort / Verlag

Netherlands: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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.