Designing highly UV-emitting lanthanide nanoscintillators for in vivo X-ray-activated tumor therapy

X-ray nanoscintillator-based photoresponsive therapy is emerging as a promising strategy to treat in vivo tumors, necessitating the development of nanoscintillators with X-ray-excited luminescence in the ultraviolet region (UV-XEL) for the photoactivation of therapeutic precursors. However, it remains a challenge to achieve high-efficiency X-ray-activated tumor therapy due to the limited UV-XEL efficacy. Herein, we developed novel Gd 3+ /Ce 3+ -codoped LiLuF 4 nanoscintillators with strong UV-XEL for in vivo tumor therapy. Significantly, through optimization of host materials, dopants, and energy transfer process, the developed nanoscintillators enabled effective enhancement of UV-XEL (up to 18-fold) as compared with the traditional Ce 3+ -doped counterparts. As a proof-of-concept study to evaluate the in vivo therapeutic applications of the nanoscintillators, we integrated them with nitric oxide (NO) precursors for controllably generating NO upon the X-ray exposure, achieving superior in vivo antitumor effect upon X-ray-induced synergetic NO therapy and radiotherapy. Moreover, X-ray-activated NO therapy can inhibit tumor metastasis into liver to suppress tumor regrowth and prolong mice survival. This work might motivate future development of X-ray nanoscintillators for treating diseases in deep tissue.