Full-Process Radiosensitization Based on Nanoscale Metal-Organic Frameworks.

Full-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 Fe ions uniformly dispersed () were constructed to integratedly improve radiotherapeutic effects a multifaceted mechanism. The experiments demonstrated that persistent reactive oxygen species stress from -activated Fenton reaction reassorted cell cycle distribution, consequently contributing to increased tumoral radiosensitivity to photon radiation. Upon irradiation during the course of radiation therapy, Hf in gave substantial amounts of high-energy electrons, which partially converted HO 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 Fe to Fe and further promoted the production of •OH in the Fenton process to attack DNA. The postponed the DNA damage response process by interfering with certain proteins involved in the DNA repair signaling pathway. The experiments showed improved radiotherapeutic effects from integrated contributions from Fe-based Fenton reaction and Hf-induced X-ray energy conversion in tumors. This work provides a nMOFs-based full-process radiosensitizing approach for better radiotherapeutic efficacy.