Gold nanoparticle doped Cuhemin nanosheets with a remodeling tumor microenvironment for multiple radiotherapy sensitization

作者:Qiao, Kun; Mo, Jianlan; Pan, You; Zhang, Shiyuan; Jiang, Cong; Lyu, Meng; Cui, Ying*; Huang, Yuanxi*; Ning, Shipeng*
来源:Journal of Materials Chemistry B, 2023, 11(18): 4095-4101.
DOI:10.1039/d2tb02806a

摘要

Effective radiosensitizers are urgently needed due to the serious negative effects that high radiation doses might have. We created an integrated nano-system (Cuhemin-Au) made of Cuhemin nanosheets and Au nanoparticles (Au NPs) for sensitizing radiotherapy to solve this issue. This system can manifest enzyme-like activities to universally suppress the resistance pathways in breast cancer cells for amplifying radiation damage. Cuhemin-Au NPs increase the energy deposition of radiation owing to the high X-ray attenuation coefficient of Au. In addition, Cuhemin-Au has peroxidase (POD)-like and glucose oxidase (Gox)-like activity, and can also consume intracellular GSH, which can reduce intracellular GSH levels to reduce tumor cells' capacity to repair DNA and deplete intracellular glucose via their characteristic Gox-like catalytic activities, which can cause an increase in the oxidative stress and further produce H2O2. Cuhemin-Au then produced OH, which upsets redox equilibrium and destroys mitochondria, leading to radiation sensitivity, after reacting with enough hydrogen peroxide in tumor cells. Cuhemin-Au combined with low dose RT (4 Gy) could significantly limit tumor development with fewer adverse effects, according to in vivo and in vitro experiments. This platform generated a fresh concept for the construction of a radiotherapy sensitization system and accomplished synergistic radiotherapy sensitization.

  • 单位
    y; 哈尔滨医科大学