The shallow penetration depth of photothermal agents in the first near-infrared (NIR-I) window significantly limits their therapeutic efficiency. Multifunctional nanotheranostic agents in the second near-infrared (NIR-II) window have drawn extensive attention for their combined treatment of tumors. Here, for the first time, we created oxygen-deficient black SnO2-x with strong NIR (700-1200 nm) light absorption with NaBH4 reduction from white SnO2. Hyaluronic acid (HA) could selectively target cancer cells overexpressed CD44 protein. After modification with HA, the obtained nanotheranostic SnO2-x@SiO2-HA showed high dispersity in aqueous solution and good biocompatibility. SnO2-x@SiO2-HA was confirmed to simultaneously generate enough hyperthermia and reactive oxygen species with single NIR-II (1064 nm) light irradiation. Because HA is highly affined to CD44 protein, SnO2-x@SiO2-HA has specific uptake by overexpressed CD44 cells and can be accurately transferred to the tumor site. Furthermore, tumor growth was significantly inhibited following synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) with targeted specificity under the guidance of photoacoustic (PA) imaging using 1064 nm laser irradiation in vivo. Moreover, SnO2-x@SiO2-HA accelerated wound healing. This work prominently extends the therapeutic utilization of semiconductor nanomaterials by changing their nanostructures and demonstrates for the first time that SnO2-x based therapeutic agents can accelerate wound healing. STATEMENT OF SIGNIFICANCE: The phototherapeutic efficacy of nanotheranostics by NIR-I lightirradiation was restricted owing to the limitation of tissue penetration and maximum permissible exposure. To overcome these limitations, we hereby fabricated a NIR-IIlight-mediated multifunctional nanotheranostic based on SnO2-x. The introduction of oxygen vacancy strategy was employed to construct full spectrum responsive oxygen-deficient SnO2-x, endowing outstanding photothermal conversion, and remarkable production activity of reactive oxygen species under NIR-II light activation. Tumor growth was significantly inhibited following synergistic PDT/PTT with targeted specificity under the guidance of photoacoustic imaging using 1064 nm laser irradiation in vivo. Our strategy not only expands the biomedical application of SnO2, but also providea method to develop other inorganic metal oxide-based nanosystems for NIR-II light-activated phototheranostic of cancers.

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