Controlling trapping states on selective theranostic core@shell (NaYF4:Yb,Tm@TiO2-ZrO2) nanocomplexes for enhanced NIR-activated photodynamic therapy against breast cancer cells

Abstract

Photodynamic and immune therapies are innovative medical strategies against cancer, and their integration with upconversion nanoparticles (UCNPs) can improve the diagnosis and treatment of the disease. The UCNPs convert the deep penetrating near-infrared (NIR) light into higher energy emissions, allowing the imaging and detection of malignant cells and the simultaneous energy transfer for activation of the photosensitizers. In this work, the UCNPs were coated with a photocatalytic TiO₂/ZrO₂ shell and an increase of oxygen defects (V_O) was observed as a result of the partial substitution of Ti⁴⁺ by Zr⁴⁺ ions in the crystalline lattice of TiO₂. Such defects act as trapping states improving charge separation and then reducing the recombination rate of the electron–hole pairs (e⁻/h⁺) generated upon resonant energy transfer from the donor (UCNPs) to acceptors (shell). The overall results are the enhancement of both ROS production and the emission band centered at 801 nm which is useful for tracking cells at the deep tissue level. However, an excess of those defects produces deleterious effects on both processes as a result of charge migration. The specificity against HER2 positive breast cancer was provided by bioconjugation with the monoclonal antibody trastuzumab. After administration of the synthesized NaYF₄:Yb,Tm@TiO₂/ZrO₂–trastuzumab theranostic nanocomplex doped with an optimal ZrO₂ molar concentration (25%) and subsequent exposure to 975 nm light (0.71 W cm⁻²) during 5 minutes, HER2-positive SKBr3 breast cancer cells were suppressed with 88% drop of the cell viability, 28% higher than UCNPs decorated with a pure TiO₂ shell.