Evaluation of Scintillating Nanoparticles for Radiotherapy and PDT

光动力疗法（PDT），其中细胞被化学光敏剂靶向，然后在用光照射时被杀死，长期以来一直是活跃的研究领域，并且也用于临床，主要用于治疗皮肤病。然而，PDT用于深部肿瘤组织受到光穿透性差的阻碍。虽然近红外光可以穿透几厘米进入组织，但目前可用的光敏剂更有效地被可见光激发，可见光迅速衰减。 为了解决这个问题，最近发表的一篇论文提出使用与光敏剂缀合的纳米颗粒进行X射线刺激的光动力学治疗。在这个系统中，x射线会激发纳米颗粒发射可见光，激发附着的光敏剂。与传统方法相比，该系统的明显优势在于X射线的深层组织穿透。此外，可能的是纳米颗粒光敏剂可以比当前的药剂更选择性地靶向肿瘤组织。 为了使所提出的方法可行，纳米颗粒-光敏剂缀合物的光毒性必须在治疗辐射剂量或更低剂量下可测量。我们组装了由比色皿保持器、准直透镜、光纤电缆、光学带通滤波器和光电倍增管组成的实验装置，并使用该装置测量了纳米颗粒样品在辐照下的光产额。我们还借鉴了PDT剂量，镧系元素光产率，镧系元素吸收和纳米颗粒吸收到靶组织的文献结果，以评估这一建议的可行性。我们的计算结果表明，对于合理的高，但可达到的光产率，这些纳米粒子共轭物可能是有用的放射增敏剂，特别是在近距离放射治疗应用的X射线能量是亚MeV。 这些计算和文献综述的结果现已发表。

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 now been published.