NIR-Driven Intracellular Photocatalytic O₂ Evolution on Z-Scheme Ni₃S₂/Cu_1.8S@HA for Hypoxic Tumor Therapy

Hypoxia in a tumor microenvironment (TME) has inhibited the photodynamic therapy (PDT) efficacy. Here, Ni₃S₂/Cu_1.8S nanoheterostructures were synthesized as a new photosensitizer, which also realizes the intracellular photocatalytic O₂ evolution to relieve hypoxia in TME and enhance PDT as well. With the narrow band gap (below 1.5 eV), the near infrared (NIR) (808 nm) can stimulate their separation of the electron-hole. The novel Z-scheme nanoheterostructures, testified by experimental data and density functional theory (DFT) calculation, possess a higher redox ability, endowing the photoexited holes with sufficient potential to oxide H₂O into O₂, directly. Meanwhile, the photostimulated electrons can capture the dissolved O₂ to form a toxic reactive oxygen species (ROS). Moreover, Ni₃S₂/Cu_1.8S nanocomposites also possess the catalase-/peroxidase-like activity to convert the endogenous H₂O₂ into ·OH and O₂, which not only cause chemodynamic therapy (CDT) but also alleviate hypoxia to assist the PDT as well. In addition, owing to the narrow band gap, they possess a high NIR harvest and great photothermal conversion efficiency (49.5%). It is noted that the nanocomposites also exhibit novel biodegradation and can be metabolized and eliminated via feces and urine within 2 weeks. The present single electrons in Ni/Cu ions induce the magnetic resonance imaging (MRI) ability for Ni₃S₂/Cu_1.8S. To make sure that the cancer cells were specifically targeted, hyaluronic acid (HA) was grafted outside and Ni₃S₂/Cu_1.8S@HA integrated photodynamic therapy (PDT), chemodynamic therapy (CDT), and photothermal therapy (PTT) to exhibit the great anticancer efficiency for hypoxic tumor elimination.