Selective Organ-Targeting Hafnium Oxide Nanoparticles with Multienzyme-Mimetic Activities Attenuate Radiation-Induced Tissue Damage

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, radiosensiti...

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Veröffentlicht in:Advanced materials (Weinheim) 2024-05, Vol.36 (19), p.e2308098-e2308098
Hauptverfasser: Liu, Dingxin, Cao, Fei, Xu, Zhifeng, Zhao, Chunhua, Liu, Zekun, Pang, Jiadong, Liu, Ze-Xian, Moghiseh, Mahdieh, Butler, Anthony, Liang, Shaoxia, Fan, Weijun, Yang, Jiang
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Sprache:eng
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Zusammenfassung: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 (HfO NPs) are rationally designed via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO NPs like Hensify are commonly radioenhancers, but SORT HfO 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 HfO 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.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.202308098