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; Ronald B Moore

doi:10.3389/fonc.2023.1244709

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

Front Oncol. 2023 Aug 28:13:1244709. doi: 10.3389/fonc.2023.1244709. eCollection 2023.

Authors

Affiliations

¹ Department of Oncology, University of Alberta, Edmonton, AB, Canada.
² Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
³ Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, United States.
⁴ Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, United States.
⁵ Department of Surgery, University of Alberta, Edmonton, AB, Canada.

Abstract

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: PDT - photodynamic therapy; PLGA (poly-lactic-co-glycolic acid); radiation; radioPDT; radiodynamic therapy; ruthenium.

Grants and funding

This research was supported by funding from the Canadian Institute of Health Research (CIHR) NFRFE-2019-01265 grant and Canadian Urologic Oncology Group (CUOG) Astellas Research Grant Program funded by Astellas Pharma Canada, Inc. and jointly established by Astellas Pharma Canada, Inc., CUOG, and the CUA, Montreal, QC. JL held the Frank and Carla Sojonky Chair in Prostate Cancer Research funded by the Alberta Cancer Foundation from 2012 to 2021. RM holds the Mr. Lube Chair in Uro-Oncology, Edmonton, AB.