Lanthanide Doped Nanoparticles for X-ray Induced Photodynamic Therapy

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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.