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

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2023-05, Vol.11 (18), p.495-411
• Main Authors: Qiao, Kun, Mo, Jianlan, Pan, You, Zhang, Shiyuan, Jiang, Cong, Lyu, Meng, Cui, Ying, Huang, Yuanxi, Ning, Shipeng
• Format: Article
• Language: English
• Subjects: Attenuation coefficients; DNA repair; Glucose Oxidase; Gold; Gold - pharmacology; Hydrogen Peroxide; Intracellular; Metal Nanoparticles; Mitochondria; Nanoparticles; Nanosheets; Oxidative stress; Oxidoreductases; Peroxidase; Radiation damage; Radiation dosage; Radiation therapy; Sensitizing; Tumor cells; Tumor Microenvironment; Tumors
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d2tb02806a

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 H 2 O 2 . Cuhemin-Au then produced &z.rad;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. We created an integrated nano-system (Cuhemin-Au) for sensitizing radiotherapy. Cuhemin-Au upsets redox equilibrium and destroys mitochondria, leading to radiation sensitivity.