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

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 (VO) 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.

An immunoconjugated up-conversion nanocomplex for selective imaging and photodynamic therapy against HER2-positive breast cancer.

Photodynamic therapy represents a very attractive therapeutic tool considered to be effective, minimally invasive and minimally toxic. However, conventional photodynamic therapy actually has two main constraints: the limited penetration depth of visible light needed for its activation, and the lack of selectivity. Considering this, this work reports the synthesis and evaluation of a novel nanoconjugate for imaging and selective photodynamic therapy against HER2-positive breast cancer, a particularly aggressive form of the disease. It was demonstrated that upon 975 nm near infrared light exposure, the red emission of the NaYF4:Yb,Er up-conversion nanoparticles (UCNPs) can be used for optical imaging and simultaneously represent the source for the excitation of a covalently bound zinc tetracarboxyphenoxy phthalocyanine (ZnPc), a photosensitizer that in turn transfers energy to ground state molecular oxygen to produce cytotoxic singlet oxygen. The specificity of our nanoconjugates was achieved by immunoconjugation with Trastuzumab (Tras), a specific monoclonal antibody for selective detection and treatment of HER2-overexpressing malignant breast cancer cells. Selective tracking of SKBR-3 HER2-positive cells was verified by confocal microscopy analysis, and the photodynamic therapy effect was considerably improved when Trastuzumab was incorporated into the nanoconjugate, the UCNPs-ZnPc-Tras being practically inert in the absence of infrared light exposure but reducing the HER2-positive cell viability up to 21% upon 5 min of the irradiation. This theranostic nanoconjugate represents a valuable alternative for HER2-positive breast cancer imaging and selective photodynamic therapy.