Evaluation of Scintillating Nanoparticles for Radiotherapy and PDT

闪烁纳米颗粒放射治疗和 PDT 的评价

• 批准号: 7967907
• 负责人: Nicole Y Morgan
• 金额: $ 0.73万
• 依托单位: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7967907
• 关键词: Address; Area; Attenuated; Brachytherapy; Cells; Chemicals; Dose; Equipment; Evaluation; Fiber Optics; Lanthanoid Series Elements; Light; Literature; Measurable; Measurement; Measures; Methods; Modeling; Optics; Paper; Penetration; Photochemotherapy; Photosensitizing Agents; Phototoxicity; Publishing; Radiation; Radiation therapy; Radiation-Sensitizing Agents; Research; Review Literature; Roentgen Rays; Sampling; System; Therapeutic; Tissues; Tube; Tumor Tissue; Visible Radiation; absorption; base; irradiation; killings; lens; light emission; nanoparticle; photomultiplier; skin disorder; uptake

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.

光动力疗法(PDT)是一种用化学光敏剂靶向细胞，然后在光照射下杀死细胞的疗法，长期以来一直是一个活跃的研究领域，也被用于临床，主要用于治疗皮肤病。然而，由于透光性差，PDT在深层肿瘤组织中的应用一直受到阻碍。尽管近红外光可以穿透组织几厘米，但目前可用的光敏剂更有效地被可见光激发，而可见光很快就会减弱。 为了解决这个问题，最近发表的一篇论文提出将闪烁纳米颗粒与光敏剂结合起来用于X射线刺激光动力疗法。在这个系统中，X射线会激发纳米颗粒的可见光发射，激发附着的光敏剂。与传统方法相比，该系统的明显优势是X射线可以深入组织穿透。此外，纳米颗粒光敏剂可能比目前的光敏剂更有选择性地靶向肿瘤组织。 为了使这种建议的方法可行，纳米颗粒-光敏剂结合物的光毒性必须在治疗性辐射剂量或更低的剂量下可测得。我们组装了由试管支架、准直透镜、光缆、光学带通滤光器和光电倍增管组成的实验装置，并利用该装置测量了纳米粒子样品在辐照下的光产额。我们还参考了有关光动力疗法剂量、镧系元素光产率、镧系元素吸收和纳米颗粒对靶组织摄取的文献结果，以评估这一建议的可行性。我们的计算结果表明，对于相当高但可获得的光产额，这些纳米粒子结合物可能作为放射增敏剂潜在地有用，特别是在X射线能量为亚MeV的近距离治疗应用中。这些计算和文献综述的结果现已发表。