Abstract

The killing effect of nitrogen-doped titanium dioxide (N-TiO2) nanoparticles on human cervical carcinoma (HeLa) cells by visible light photodynamic therapy (PDT) was higher than that of TiO2 nanoparticles. To study the mechanism of the killing effect, the reactive oxygen species produced by the visible-light-activated N-TiO2 and pure-TiO2 were evaluated and compared. The changes of the cellular parameters, such as the mitochondrial membrane potential (MMP), intracellular Ca2+, and nitrogen monoxide (NO) concentrations after PDT were measured and compared for N-TiO2- and TiO2-treated HeLa cells. The N-TiO2 resulted in more loss of MMP and higher increase of Ca2+ and NO in HeLa cells than pure TiO2. The cell morphology changes with time were also examined by a confocal microscope. The cells incubated with N-TiO2 exhibited serious distortion and membrane breakage at 60 min after the PDT.

Highlights

  • In recent years, semiconductor titanium dioxide (TiO2) was noticed as a potential photosensitizer in the field of photodynamic therapy (PDT) due to its low toxicity, high stability, excellent biocompatibility, and photoreactivity [1,2,3,4]

  • The electrons in the valence band of TiO2 can be excited to the conduction band by ultraviolet (UV) radiation with the wavelength shorter than 387 nm, resulting in the photoinduced hole-electron pairs. These photoinduced electrons and holes can interact with surrounding H2O or O2 molecules and generate various reactive oxygen species (ROS, such as superoxide anion radical O2 ·− [5], hydroxyl radical OH · [6], singlet oxygen 1O2 [7], and hydrogen peroxide H2O2 [8]), which can react with biological molecules, such as lipids, proteins, and DNA, cause their damages, and eventually kill cancer cells [1,9,10]

  • It means that nitrogen-doped TiO2 (N-TiO2) could generate more ROS than TiO2 under visible light irradiation, which agrees well with the spectral result that N-TiO2 showed higher visible light absorption than TiO2

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Summary

Introduction

Semiconductor titanium dioxide (TiO2) was noticed as a potential photosensitizer in the field of photodynamic therapy (PDT) due to its low toxicity, high stability, excellent biocompatibility, and photoreactivity [1,2,3,4]. The electrons in the valence band of TiO2 can be excited to the conduction band by ultraviolet (UV) radiation with the wavelength shorter than 387 nm (corresponding to 3.2 eV as the band gap energy of anatase TiO2), resulting in the photoinduced hole-electron pairs These photoinduced electrons and holes can interact with surrounding H2O or O2 molecules and generate various reactive oxygen species (ROS, such as superoxide anion radical O2 ·− [5], hydroxyl radical OH · [6], singlet oxygen 1O2 [7], and hydrogen peroxide H2O2 [8]), which can react with biological molecules, such as lipids, proteins, and DNA, cause their damages, and eventually kill cancer cells [1,9,10]. In our previous study [10], we enhanced the visible light absorption of TiO2 by nitrogen doping and found that the nitrogen-doped TiO2 (N-TiO2) showed much higher visible-light-induced photokilling effects on cancer cells than the pure TiO2

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