DNA损伤
生物物理学
活性氧
细胞生物学
纳米技术
材料科学
癌症研究
化学
生物
生物化学
DNA
作者
Dingxin Liu,Fei Cao,Zhifeng Xu,Chunhua Zhao,Zexian Liu,Jiangli Pang,Zexian Liu,Mahdieh Moghiseh,Anthony Butler,Shaoxia Liang,Weijun Fan,Jiang Yang
标识
DOI:10.1002/adma.202308098
摘要
Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, radiosensitivity indices are evaluated of diverse normal organs as a genomic predictor of radiation susceptibility. Selective ORgan-Targeting (SORT) hafnium oxide nanoparticles (HfO2 NPs) are rationally designed via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO2 NPs like Hensify are commonly radioenhancers, but SORT HfO2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. A universal methodology is proposed to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition.
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