4.5 Article

Tb-Doped core-shell-shell nanophosphors for enhanced X-ray induced luminescence and sensitization of radiodynamic therapy

Journal

BIOMATERIALS SCIENCE
Volume 9, Issue 2, Pages 496-505

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm00897d

Keywords

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Funding

  1. NIH NIGMS as a Maximizing Investigators' Research Award [1R35GM119839-01]
  2. Oregon State University College of Pharmacy Start-up Funds
  3. Portland State University (PSU) faculty development program
  4. National Science Foundation [DMR-0923572]

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The development of radiation responsive materials, such as nanoscintillators, has led to exciting new theranostic applications, particularly in X-ray luminescence computed tomography. A radioluminescent nanoplatform consisting of Tb-doped nanophosphors with a unique core/shell/shell (CSS) architecture has shown bright optical luminescence under X-ray excitation and potential for enhanced DNA damage and cell killing in combination with X-ray irradiation.
The development of radiation responsive materials, such as nanoscintillators, enables a variety of exciting new theranostic applications. In particular, the ability of nanophosphors to serve as molecular imaging agents in novel modalities, such as X-ray luminescence computed tomography (XLCT), has gained significant interest recently. Here, we present a radioluminescent nanoplatform consisting of Tb-doped nanophosphors with an unique core/shell/shell (CSS) architecture for improved optical emission under X-ray excitation. Owing to the spatial confinement and separation of luminescent activators, these CSS nanophosphors exhibited bright optical luminescence upon irradiation. In addition to standard physiochemical characterization, these CSS nanophosphors were evaluated for their ability to serve as energy mediators in X-ray stimulated photodynamic therapy, also known as radiodynamic therapy (RDT), through attachment of a photosensitizer, rose bengal (RB). Furthermore, cRGD peptide was used as a model targeting agent against U87 MG glioblastoma cells. In vitro RDT efficacy studies suggested the RGD-CSS-RB in combination with X-ray irradiation could induce enhanced DNA damage and increased cell killing, while the nanoparticles alone are well tolerated. These studies support the utility of CSS nanophosphors and warrants their further development for theranostic applications.

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