Frontiers in Oncology (Aug 2023)

High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy

  • Abul Kalam Azad,
  • Lothar Lilge,
  • Nawaid H. Usmani,
  • John D. Lewis,
  • Houston D. Cole,
  • Colin G. Cameron,
  • Sherri A. McFarland,
  • Deepak Dinakaran,
  • Deepak Dinakaran,
  • Ronald B. Moore,
  • Ronald B. Moore

DOI
https://doi.org/10.3389/fonc.2023.1244709
Journal volume & issue
Vol. 13

Abstract

Read online

Traditional external light-based Photodynamic Therapy (PDT)’s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in penetrating deep-seated tumors. To address this, the emerging field of radiation-activated PDT (radioPDT) uses X-rays to trigger photosensitizer-containing nanoparticles (NPs). A key consideration in radioPDT is the energy transfer efficiency from X-rays to the photosensitizer for ultimately generating the phototoxic reactive oxygen species (ROS). In this study, we developed a new variant of pegylated poly-lactic-co-glycolic (PEG-PLGA) encapsulated nanoscintillators (NSCs) along with a new, highly efficient ruthenium-based photosensitizer (Ru/radioPDT). Characterization of this NP via transmission electron microscopy, dynamic light scattering, UV-Vis spectroscopy, and inductively coupled plasma mass-spectroscopy showed an NP size of 120 nm, polydispersity index (PDI) of less than 0.25, high NSCs loading efficiency over 90% and in vitro accumulation within the cytosolic structure of endoplasmic reticulum and lysosome. The therapeutic efficacy of Ru/radioPDT was determined using PC3 cell viability and clonogenic assays. Ru/radioPDT exhibited minimal cell toxicity until activated by radiation to induce significant cancer cell kill over radiation alone. Compared to protoporphyrin IX-mediated radioPDT (PPIX/radioPDT), Ru/radioPDT showed higher capacity for singlet oxygen generation, maintaining a comparable cytotoxic effect on PC3 cells.

Keywords