Full-spectrum responsive ZrO2-based phototheranostic agent for NIR-II photoacoustic imaging-guided cancer phototherapy

Abstract

Second near-infrared (NIR-II) window responsive phototheranostic agents have a precise spatiotemporal potential for the diagnosis and treatment of cancer. In this study, a full-spectrum responsive ZrO₂-based phototheranostic agent was found to achieve NIR-II photoacoustic (PA) imaging-guided tumour-targeting phototherapy. Initially, the ZrO₂-based phototheranostic agent was fabricated through NaBH₄ reduction to form boron-doped oxygen-deficient zirconia (ZrO_2−x-B), an amino-functionalised SiO₂ shell and a further covalent connection with hyaluronic acid (HA), namely, ZrO_2−x-B@SiO₂-HA. In the ZrO_2−x-B@SiO₂-HA system, the oxygen vacancy and boron doping resulted in full-spectrum absorption, enabling a high NIR-II photothermal conversion, high-resolution PA imaging ability and a remarkable production of reactive oxygen species (ROS). The surface modification of HA provided ZrO_2−x-B@SiO₂-HA with water dispersibility and a targeting capability for CD44 overexpressed cancer cells. Furthermore, in vitro and in vivo experiments showed that NIR-II activated ZrO_2−x-B@SiO₂-HA had a targeted photothermal/photodynamic effect for cancer elimination under the real-time guidance of NIR-II PAs. Hence, ZrO_2−x-B@SiO₂-HA displays a precise NIR-II radiation-activated phototheranostic potential for PA imaging-guided cancer-targeting photothermal/photodynamic therapy.