Full-spectrum responsive WO_3−x@HA nanotheranostics for NIR-II photoacoustic imaging-guided PTT/PDT/CDT synergistic therapy

The selection of second near-infrared (NIR-II) window-responsive nanotheranostics is significant for precise cancer treatments. In this work, a full-spectrum responsive multifunctional WO₃-based nanotheranostic was produced to accomplish NIR-II photoacoustic (PA) imaging-guided photothermal therapy (PTT), photodynamic therapy (PDT) and chemodynamic therapy (CDT) synergistic therapy. For this purpose, oxygen vacancies were formed in WO₃, which narrows the band gap and allows WO_3−x to absorb over the full spectrum. The WO_3−x@HA nanotheranostic was constructed with the successive surface modification of hyaluronic acid (HA) to improve the water dispersibility and tumour targeting efficiency. Upon activation with NIR-II irradiation, WO_3−x@HA showed excellent photothermal conversion, reactive oxygen species (ROS) production and a high-resolution photoacoustic (PA) imaging ability. Meanwhile, WO_3−x@HA exhibited both Fenton-like reaction and glutathione (GSH) depletion properties; the effective photothermal conversion ability of WO_3−x@HA elevates the local temperature and accelerates the Fenton-like process to achieve enhanced PTT/PDT/CDT. The formation of oxygen vacancies was proved to be key to the photothermal, photodynamic and chemodynamic properties of WO_3−x@HA, and the corresponding possible mechanisms were proposed. In vitro and in vivo experiments have confirmed that WO_3−x@HA has a PTT/PDT/CDT synergistic therapy effect for tumour ablation under real-time NIR-II PA imaging guidance. Therefore, WO_3−x@HA reveals the potential for NIR-II irradiation-activated precise theranostics for PA imaging-guided tumour-targeting PTT/PDT/CDT synergistic therapy.