High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy
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 ph...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1244709/full |
| _version_ | 1827859238828900352 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Abul Kalam Azad |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T13:05:32Z |
| format | Article |
| id | doaj.art-89781f0f63ab417a95092c6c120eee6e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T13:05:32Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-89781f0f63ab417a95092c6c120eee6e2023-08-28T15:52:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.12447091244709High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic TherapyAbul Kalam Azad0Lothar Lilge1Nawaid H. Usmani2John D. Lewis3Houston D. Cole4Colin G. Cameron5Sherri A. McFarland6Deepak Dinakaran7Deepak Dinakaran8Ronald B. Moore9Ronald B. Moore10Department of Oncology, University of Alberta, Edmonton, AB, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, CanadaDepartment of Oncology, University of Alberta, Edmonton, AB, CanadaDepartment of Oncology, University of Alberta, Edmonton, AB, CanadaDepartment of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, United StatesDepartment of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, United StatesDepartment of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, United StatesDepartment of Oncology, University of Alberta, Edmonton, AB, CanadaRadiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, United StatesDepartment of Oncology, University of Alberta, Edmonton, AB, CanadaDepartment of Surgery, University of Alberta, Edmonton, AB, CanadaTraditional 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1244709/fullradioPDTradiodynamic therapyPDT - photodynamic therapyradiationPLGA (poly-lactic-co-glycolic acid)ruthenium |
| spellingShingle | 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 High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy Frontiers in Oncology radioPDT radiodynamic therapy PDT - photodynamic therapy radiation PLGA (poly-lactic-co-glycolic acid) ruthenium |
| title | High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy |
| title_full | High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy |
| title_fullStr | High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy |
| title_full_unstemmed | High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy |
| title_short | High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy |
| title_sort | high quantum efficiency ruthenium coordination complex photosensitizer for improved radiation activated photodynamic therapy |
| topic | radioPDT radiodynamic therapy PDT - photodynamic therapy radiation PLGA (poly-lactic-co-glycolic acid) ruthenium |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1244709/full |
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