Novel photodynamic therapy using two-dimensional NiPS₃ nanosheets that target hypoxic microenvironments for precise...

Photodynamic therapy (PDT) is a highly promising modality against cancer, but its efficacy is severely limited by the low oxygen content in solid tumors. In this study, a smart photosensitive NiPS₃ nanosheet was developed to solve the problem of low oxygen to allow PDT to be performed against tumors. The photosensitized ROS generation mechanism of NiPS₃ is the photon-generated electron-hole pathway, which can generate O₂ ^·- and ·OH at the conduction band and valance band, respectively. More crucial is that ·OH generation doesn't need O₂, and the O₂ ^·- can also work in a low O₂ environment, and depleting oxygen in tumor cells. Modified with triphenylphosphine (TPP) and based on density functional theory (DFT) calculations and experimental data, the NiPS₃@TPP nano-system underwent targeted action toward mitochondria. In vitro experiments demonstrated that the reactive oxygen species (ROS) produced by NiPS₃@TPP altered mitochondrial membrane permeability, which not only prolonged the PDT effect but also resulted in mitochondria apoptosis pathways inducing an apoptosis cascade. In vivo experiments demonstrated the targeting capability with low toxicity of the NiPS₃@TPP nano-system. Tumor targeting at the tested dose indicated that it represented a promising biocompatible photosensitizer for in vivo biomedical applications.