UV-Emitting Upconversion-Based TiO₂ Photosensitizing Nanoplatform: Near-Infrared Light Mediated <i>in Vivo</i> Photodynamic Therapy <i>via</i> Mitochondria-Involved Apoptosis Pathway

Photodynamic therapy (PDT) is a promising antitumor treatment that is based on the photosensitizers that inhibit cancer cells by yielding reactive oxygen species (ROS) after irradiation of light with specific wavelengths. As a potential photosensitizer, titanium dioxide (TiO₂) exhibits minimal dark cytotoxicity and excellent ultraviolet (UV) light triggered cytotoxicity, but is challenged by the limited tissue penetration of UV light. Herein, a novel near-infrared (NIR) light activated photosensitizer for PDT based on TiO₂-coated upconversion nanoparticle (UCNP) core/shell nanocomposites (UCNPs@TiO₂ NCs) is designed. NaYF₄:Yb³⁺,Tm³⁺@NaGdF₄:Yb³⁺ core/shell UCNPs can efficiently convert NIR light to UV emission that matches well with the absorption of TiO₂ shells. The UCNPs@TiO₂ NCs endocytosed by cancer cells are able to generate intracellular ROS under NIR irradiation, decreasing the mitochondrial membrane potential to release cytochrome <i>c</i> into the cytosol and then activating caspase 3 to induce cancer cell apoptosis. NIR light triggered PDT of tumor-bearing mice with UCNPs@TiO₂ as photosensitizers can suppress tumor growth efficiently due to the better tissue penetration than UV irradiation. On the basis of the evidence of <i>in vitro</i> and <i>in vivo</i> results, UCNPs@TiO₂ NCs could serve as an effective photosensitizer for NIR light mediated PDT in antitumor therapy