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/Cu1.8S 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/Cu1.8S 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/Cu1.8S. To make sure that the cancer cells were specifically targeted, hyaluronic acid (HA) was grafted outside and Ni3S2/Cu1.8S@HA integrated photodynamic therapy (PDT), chemodynamic therapy (CDT), and photothermal therapy (PTT) to exhibit the great anticancer efficiency for hypoxic tumor elimination.