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

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:Yb(3+),Tm(3+)@NaGdF4:Yb(3+) 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.

Polyaniline-coated upconversion nanoparticles with upconverting luminescent and photothermal conversion properties for photothermal cancer therapy

“…[32][33][34][35][36][37][38] Therefore, UCNPs have been recently used as building blocks in the construction of multimodal contrast agents for imagingguided therapy. [39][40][41][42][43][44][45] In the current study, upconversion nanoparticles (UCNPs) were first prepared by a typical solvothermal method. A polyaniline photothermal therapeutic shell was then formed by the polymerization of an aniline monomer in acid aqueous conditions, thereby obtaining polyaniline-coated UCNPs (UCNPs-PANPs).…”

Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

“…The antiapoptotic protein Bcl-2 can counteract the proapoptotic activity from Bax, and the ratio of Bax/Bcl-2 might be another useful factor in the cellular threshold for undergoing apoptosis induced by PDT. 45 Many studies have shown that activation of the caspase protein family triggers the apoptotic process in cells. Caspase-9 cleaved and activated procaspase-3.…”

Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides

“…The reduced ratio of red to green fluorescence intensity can be calculated as ∆Ψ m , which indicates mitochondrial depolarization. 62,63 As shown in Figure 5A and B, the ∆Ψ m of the blank RGD-KLA-Liptreated group was 99.08%±1.67% of control (culture medium only), indicating that the blank RGD-KLA-Lips had no effect on the mitochondria. After treatment with Taxol, RGD/PTXLips, KLA/PTX-Lips or RGD-KLA/PTX-Lips for 10 h, the ∆Ψ m was 67.99%±6.78%, 73.65%±1.92%, 39.91%±0.40% and 19.73%±1.27% of control, respectively.…”