Hyaluronic Acid-Functionalized Bismuth Vanadate/Molybdenum Disulfide Nanoheterojunctions Achieve Efficient Phototherapy of Hypoxic Tumor.

Photodynamic therapy (PDT) is a promising cancer treatment modality due to its minimally invasive nature and spatiotemporal selectivity. However, its effectiveness is substantially hindered by tumor hypoxia. In this study, bismuth vanadate/molybdenum disulfide@hyaluronic acid (BiVO₄/MoS₂@HA, BM@HA) nanoparticles were engineered to overcome the challenges of tumor hypoxia in PDT. The formation of p-n heterojunctions between MoS₂ and BiVO₄ facilitated electron transfer from MoS₂ to BiVO₄, imparting BM@HA with photothermal properties in the near-infrared (NIR) region and achieving an improved photothermal efficiency of 51.9%. After 808-nm laser irradiation, the electron transfers and the energy generated by photothermal effects enhanced the separation of electron-hole pairs in BM@HA, leading to the production of reactive oxygen species and the hydrolysis of oxygen. Animal experiments revealed the strong tumor-targeting capability of BM@HA, as shown by tumor photothermal imaging and in vivo small-animal imaging. Following 808-nm laser irradiation, it enabled precise tumor phototherapy by combining PDT with photothermal therapy. Furthermore, proteomic analysis revealed that BM@HA + NIR may induce necroptosis of tumor cells by activating peptidylprolyl isomerase D-related pathways. In summary, the BM@HA photosensitizer facilitated NIR photocatalytic oxygen hydrolysis, overcoming the hypoxia limitation in PDT. When combined with photothermal therapy, it displayed improved antitumor efficacy, offering a new strategy for the treatment of oral squamous cell carcinoma.