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

TLDR

Photodynamic therapy relies on photosensitizers that generate reactive oxygen species upon light irradiation; titanium dioxide is a promising candidate with low dark toxicity and UV‑triggered cytotoxicity, but its clinical use is limited by the poor tissue penetration of UV light. The study aims to develop a near‑infrared‑activated photosensitizer by coating upconversion nanoparticles with TiO2 to enable NIR‑mediated photodynamic therapy. Upconversion nanoparticles convert NIR light to UV emission that excites the TiO2 shell, producing intracellular ROS that depolarizes mitochondria, releases cytochrome c, and activates caspase‑3 to trigger apoptosis. In tumor‑bearing mice, NIR‑activated UCNPs@TiO2 suppressed tumor growth more effectively than UV irradiation, demonstrating that these nanocomposites are an effective photosensitizer for NIR‑mediated photodynamic antitumor therapy.

Abstract

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 c 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 in vitro and in vivo results, UCNPs@TiO2 NCs could serve as an effective photosensitizer for NIR light mediated PDT in antitumor therapy.