nn9b07898_si_001.pdf (3.39 MB)
Full-Process Radiosensitization Based on Nanoscale Metal–Organic Frameworks
journal contribution
posted on 2020-03-12, 17:36 authored by Teng Gong, Yanli Li, Bin Lv, Han Wang, Yanyan Liu, Wei Yang, Yelin Wu, Xingwu Jiang, Hongbo Gao, Xiangpeng Zheng, Wenbo BuFull-process
radiosensitization, that is, pre-increasing radiation
sensitivity of cancer cells, magnifying •OH formation during
ionizing irradiation, and intervention on the resultant DNA repair
for final cells death, could enhance the overall radiotherapeutic
effects, but has not yet been achieved. Herein, Hf-nMOFs with Fe3+ ions uniformly dispersed (Hf-BPY-Fe) were constructed
to integratedly improve radiotherapeutic effects via a multifaceted mechanism. The in vitro experiments
demonstrated that persistent reactive oxygen species stress from Hf-BPY-Fe-activated in situ Fenton reaction
reassorted cell cycle distribution, consequently contributing to increased
tumoral radiosensitivity to photon radiation. Upon irradiation during
the course of radiation therapy, Hf4+ in Hf-BPY-Fe gave substantial amounts of high-energy electrons, which partially
converted H2O to •OH and, meanwhile, relaxed to
a low-energy state in nMOF pores, leading to an electron-rich environment.
These aggregated electrons facilitated the reduction from Fe3+ to Fe2+ and further promoted the production of •OH
in the Fenton process to attack DNA. The Hf-BPY-Fe postponed
the DNA damage response process by interfering with certain proteins
involved in the DNA repair signaling pathway. The in vivo experiments showed improved radiotherapeutic effects from integrated
contributions from Fe3+-based Fenton reaction and Hf4+-induced X-ray energy conversion in tumors. This work provides
a nMOFs-based full-process radiosensitizing approach for better radiotherapeutic
efficacy.