Lanthanide Doped Nanoparticles for X-ray Induced Photodynamic Therapy

光穿透深度的限制阻碍了光动力疗法在深层次肿瘤中的应用。X射线激发光动力疗法(X-PDT)是基于X射线激活的发光纳米颗粒，为内脏器官的光动力疗法提供了一种新的策略。该项目的总体目标是开发一类新的纳米药物，包括辐射发光纳米颗粒和被称为光敏剂的光激活药物。在没有辐射的情况下，单个成分名义上是无毒的，这使得这是一种仅在目标体积中有效的辐射门控干预。建议的研究包括两个主要目标：(I)优化纳米药物配方和(Ii)将优化的配方应用于一组膀胱细胞系，以评估X-PDT在临床化疗和放射治疗中的潜力。重点研究了以孟加拉玫瑰为光敏剂的六方相Na(Lu，Gd)F4：Tb3+纳米晶组成的纳米体系。稀土掺杂纳米粒子具有发射带窄、激发态寿命长、反斯托克斯位移大、抗光漂白能力强、毒性低等优点，受到人们的广泛关注。作为掺杂剂的稀土离子非常适合作为闪烁材料，因为它们具有高的原子序数和合适的电子能态，可以在电磁光谱的紫外区、可见光区和近红外区发射光子。这些纳米结合物具有很高的胶体稳定性和生物相容性，可以在外部X射线照射下通过有效的能量传递产生合理的细胞毒性单线态氧(1O2)，这使得它们在深层次肿瘤的诊断和光动力学治疗中具有潜在的应用前景。

The limitation of light penetration depth hampers the application of photodynamic therapy in deep-seated tumors. X-ray excited photodynamic therapy (X-PDT), which is based on X-rays activated luminescent nanoparticles, provides a novel strategy for photodynamic therapy in internal organs. The overall goal of the project is to develop a new class of nanomedicines consisting of radioluminescent nanoparticles coupled with light-activated drugs known as photosensitizers. In the absence of radiation, the individual components are nominally non-toxic, making this a radiation-gated intervention that is only active in the target volume. The proposed research consists of primary two pursuits: (i) optimization of nanomedicine formulation and (ii) the application of the optimized formulation to a panel of bladder cell lines to evaluate the potential of X-PDT for clinical chemo-radiotherapy. The focus will be on the nanosystem consisting of hexagonal phase ß-Na(Lu,Gd)F4: Tb3+ nanocrystals combined with rose Bengal as the photosensitizer. Lanthanide doped nanoparticles are of great interest, owing to their narrow emission bands, long-lived excited states, large anti-Stokes shifts, high resistance to photobleaching, and low toxicity. Lanthanide ions as dopants are excellent for scintillation materials, as they have high atomic number and suitable electronic energy states to emit photons in the UV, visible, and near-infrared region of the electromagnetic spectrum. These nanoconjugates with a high colloidal stability and biocompatibility can generate a reasonable amount of cytotoxic singlet oxygen (1O2) through efficient energy transfer upon external X-ray radiation, which enables them to be potentially applied in diagnosis and photodynamic therapy for deep seated tumor.