Novel Photodynamic Therapy Using Two-dimensional NiPS Nanosheets That Target Hypoxic Microenvironments for Precise Cancer Treatment

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