2D MOFs nanosheets derived from 2D LDHs as a multifunctional sensitizer for sono-photodynamic therapy-mediated tumor treatment

Abstract

Sono-photodynamic therapy (SPDT) has been proposed as a new cancer treatment modality to compensate the shortcomings of limited tissue penetration depth of light in photodynamic therapy (PDT) and low reactive oxygen species (ROS) generation efficiency in sonodynamic therapy (SDT). However, the lack of favorable sensitizers with efficient PDT and SDT properties as well as high ROS yield remains a significant challenge in achieving superior therapeutic outcomes for superficial and deep tumors. Herein, we first report the construction of two-dimensional (2D) ZnAl-TCPP metal organic framework (MOF) nanosheets using ZnAl-layered double hydroxide (ZnAl-LDH) nanosheets as a precursor through phase transformation strategy for highly efficient SPDT. ZnAl-LDH nanosheets are pre-synthesized by bottom-up method and then transformed into ZnAl-TCPP nanosheets via a hydrothermal treatment with TCPP ligands. Surprisingly, ZnAl-TCPP nanosheets exhibit excellent ROS-generating activity under both light and US irradiation, which is superior than either light or US irradiation alone, demonstrating its synergistic effect for SPDT. More importantly, the ROS generation activity of ZnAl-TCPP nanosheets outperforms TCPP (3.0 times), which may be attributed to the phase transformation from LDH to MOF resulting in the decrease of bandgap, the generation of defects, and the coupling effect between heterometallic centers that sensitize TCPP ligands. After modification with polyethylene glycol (PEG), ZnAl-TCPP-PEG induces strong oxidative stress under light and US irradiation, which causes significant mitochondrial and lysosomal damage, thus leading to cell apoptosis and tumor growth inhibition.