Evaluation of Scintillating Nanoparticles for Radiotherapy and PDT

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Photodynamic therapy (PDT), in which cells are targeted with a chemical photosensitizer and then killed when irradiated with light, has been long been an area of active research, and is also used clinically, primarily to treat skin disease. However, the use of PDT for deep tumor tissues has been hampered by poor light penetration. Although near-infrared light can penetrate several centimeters into tissue, the currently available photosensitizers are much more efficiently excited by visible light, which is rapidly attenuated. To address this problem, a recently published paper proposed using scintillating nanoparticles conjugated to photosensitizers for x-ray stimulated photodynamic therapy. In this system, the x-rays would stimulate visible light emission from the nanoparticles, exciting the attached photosensitizers. The obvious advantage of this system over conventional methods is the deep tissue penetration of x-rays. In addition, it is possible that a nanoparticle photosensitizing agent could be more selectively targeted to tumor tissue than current agents. In order for this proposed method to be feasible, the phototoxicity of the nanoparticle-photosensitizer conjugates must be measurable at therapeutic radiation doses or below. We assembled experimental apparatus consisting of a cuvette holder, collimating lenses, a fiber optic cable, an optical bandpass filter and a photomultiplier tube, and used this equipment to measure the light yield of nanoparticle samples under irradiation. We also drew on results from the literature for PDT dose, lanthanide light yields, lanthanide absorption and nanoparticle uptake into targeted tissue to evaluate the feasibility of this proposal. The results of our calculations suggest that for reasonably high but attainable light yields, these nanoparticle conjugates could potentially be useful as radiosensitizers, especially in brachytherapy applications for which the X-ray energies are sub-MeV. These calculations and results from the literature review have been written up for publication, and are currently in press.