Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF 4 :Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOO − ). By simply adjusting the Ce 3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOO − in the tumor. Obtained ONOO − effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOO − , and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOO − to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy.

The malignant tumor is one of the mainly diseases leading to death, and the vigorous development of nanotechnology has opened up new frontiers for antitumor therapy. The process of researchers...

The sensitization performance of sonosensitizers plays a key role in the sonodynamic therapy (SDT) effect. Herein, ZnSnO3:Nd nanoparticles with R3c phase/amorphous heterogeneous structure are developed by phase engineering strategy and applied as an ideal sonosensitizer. In the crystalline perovskite‐type ZnSnO3:Nd, the substitution of the Zn2+ with Nd3+ causes the O 2p non‐bonded state to move toward the Fermi level, which optimizes the band structure for ultrasound sensitization by reducing bandgap. Meanwhile, the unequal charge substitution can also form electron traps and oxygen vacancies to shorten the electron migration distance, which accelerates the electron–hole separation and inhibits carrier recombination, thus improving the acoustic sensitivity. Moreover, the dangling bonds exposed on the surface of amorphous ZnSnO3:Nd provide more active sites, and the localized states of the amorphous phase may also promote carrier separation, resulting in synergistic SDT effect. In particular, the Zn2+ released from ZnSnO3:Nd in the acidic tumor microenvironment (TME) reduces the adenosine triphosphate production by inhibiting the electron transport chain , which promotes the tumor cell apoptosis through destroying the redox balance of TME. Combining the inherent second near infrared and computed tomography imaging capabilities, this ZnSnO3:Nd nanoplatform shows a promising perspective in clinic SDT field.

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