Abstract
Traditional photodynamic therapy (PDT) is limited by the penetration depth of visible light. Although the light source has been changed to near infrared, infrared light is unable to overcome the penetration barrier and it is only effective at the surface of the tumors. In this study, we used X-ray as a light source for deep-seated tumor treatment. A particle with a narrow band gap when exposed to soft X-rays would produce reactive oxygen species (ROS) to kill tumor cell, with less damage to the normal tissues. Anatase TiO2 has been studied as a photosensitizer in PDT. In the experiment, C was doped into the anatase lattice at an optimum atomic ratio to make the band gap narrower, which would be activated by X-ray to produce more ROS and kill tumor cells under stress. The results showed that the synthesized TiO2:C particles were identified as crystal structures of anatase. The synthesized particles could be activated effectively by soft X-rays to produce ROS, to degrade methylene blue by up to 30.4%. Once TiO2:C was activated by X-ray irradiation, the death rate of A549 cells in in vitro testing was as high as 16.57%, on day 2. In the animal study, the tumor size gradually decreased after treatment with TiO2:C and exposure to X-rays on day 0 and day 8. On day 14, the tumor declined to nearly half of its initial volume, while the tumor in the control group was twice its initial volume. After the animal was sacrificed, blood, and major organs were harvested for further analysis and examination, with data fully supporting the safety of the treatment. Based on the results of the study, we believe that TiO2:C when exposed to X-rays could overcome the limitation of penetration depth and could improve PDT effects by inhibiting tumor growth effectively and safely, in vivo.
Highlights
In clinical applications, photodynamic therapy (PDT) has been a common method of tumor lesion treatment, where a photosensitizer is excited by light of specific wavelengths to induce the formation of reactive oxygen species (ROS), selectively directing tumor cells towards death [1,2]
The specific aim of this study was to synthesize carbon-doped TiO2 (TiO2:C) to act as the photosensitizer in low-dose X-ray-induced PDT to overcome the limitations of penetration depth and radiation dose
X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy were performed for crystal structure identification, surface morphology observation, lattice imaging, composition analysis, and surface chemical analysis, respectively
Summary
Photodynamic therapy (PDT) has been a common method of tumor lesion treatment, where a photosensitizer is excited by light of specific wavelengths to induce the formation of reactive oxygen species (ROS), selectively directing tumor cells towards death [1,2]. The light penetration depth, limits the therapeutic efficacy of PDT. Most absorbance bands of the photosensitizers located in the range of visible light, result in penetration depths of less than 1 cm [5]. The use of two-photon excitation of nanoparticle-based photosensitizers activated by near-infrared red light could improve the penetration depth to 3 cm, it can only treat the surface of cancer cells and cannot be effectively used for deep-seated tumors [6]. In order to overcome this limitation, Chen et al proposed luminol, which is a chemical exhibiting chemo-luminescence, to be used as the in situ light source to activate 5-aminolevulinic acid (5-ALA), and meso-tetraphenylporphyrin in 5-ALA mediated the photodynamic treatment of Caco-2 cells. The excitation was indirect and less effective because of the low intensity [7]
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