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Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics
Photodynamic therapy (PDT), which involves the generation of reactive oxygen species (ROS) through interactions of a photosensitizer (PS) with light and oxygen, has been applied in oncology. Over the years, PDT techniques have been developed for the treatment of deep-seated cancers. However, (1) the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295068/ https://www.ncbi.nlm.nih.gov/pubmed/32550902 http://dx.doi.org/10.7150/thno.41752 |
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author | Chuang, Yao-Chen Chu, Chia-Hui Cheng, Shih-Hsun Liao, Lun-De Chu, Tsung-Sheng Chen, Nai-Tzu Paldino, Arthur Hsia, Yu Chen, Chin-Tu Lo, Leu-Wei |
author_facet | Chuang, Yao-Chen Chu, Chia-Hui Cheng, Shih-Hsun Liao, Lun-De Chu, Tsung-Sheng Chen, Nai-Tzu Paldino, Arthur Hsia, Yu Chen, Chin-Tu Lo, Leu-Wei |
author_sort | Chuang, Yao-Chen |
collection | PubMed |
description | Photodynamic therapy (PDT), which involves the generation of reactive oxygen species (ROS) through interactions of a photosensitizer (PS) with light and oxygen, has been applied in oncology. Over the years, PDT techniques have been developed for the treatment of deep-seated cancers. However, (1) the tissue penetration limitation of excitation photon, (2) suppressed efficiency of PS due to multiple energy transfers, and (3) insufficient oxygen source in hypoxic tumor microenvironment still constitute major challenges facing the clinical application of PDT for achieving effective treatment. We present herein a PS-independent, ionizing radiation-induced PDT agent composed of yttrium oxide nanoscintillators core and silica shell (Y(2)O(3):Eu@SiO(2)) with an annealing process. Our results revealed that annealed Y(2)O(3):Eu@SiO(2) could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y(2)O(3):Eu@SiO(2) was demonstrated to enable the generation of electron-hole (e(-)-h(+)) pairs in Y(2)O(3) under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y(2)O(3):Eu@SiO(2) with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation ((S)O(2)) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y(2)O(3):Eu@SiO(2), achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y(2)O(3):Eu@SiO(2) exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y(2)O(3):Eu@SiO(2) concentration in vivo. With the pronounced X-RL for in-vivo imaging and dosimetry, it possesses significant potential for utilization as a precision theranostics producing highly efficient X-ray PDT for deep-seated tumors. |
format | Online Article Text |
id | pubmed-7295068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-72950682020-06-17 Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics Chuang, Yao-Chen Chu, Chia-Hui Cheng, Shih-Hsun Liao, Lun-De Chu, Tsung-Sheng Chen, Nai-Tzu Paldino, Arthur Hsia, Yu Chen, Chin-Tu Lo, Leu-Wei Theranostics Research Paper Photodynamic therapy (PDT), which involves the generation of reactive oxygen species (ROS) through interactions of a photosensitizer (PS) with light and oxygen, has been applied in oncology. Over the years, PDT techniques have been developed for the treatment of deep-seated cancers. However, (1) the tissue penetration limitation of excitation photon, (2) suppressed efficiency of PS due to multiple energy transfers, and (3) insufficient oxygen source in hypoxic tumor microenvironment still constitute major challenges facing the clinical application of PDT for achieving effective treatment. We present herein a PS-independent, ionizing radiation-induced PDT agent composed of yttrium oxide nanoscintillators core and silica shell (Y(2)O(3):Eu@SiO(2)) with an annealing process. Our results revealed that annealed Y(2)O(3):Eu@SiO(2) could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y(2)O(3):Eu@SiO(2) was demonstrated to enable the generation of electron-hole (e(-)-h(+)) pairs in Y(2)O(3) under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y(2)O(3):Eu@SiO(2) with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation ((S)O(2)) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y(2)O(3):Eu@SiO(2), achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y(2)O(3):Eu@SiO(2) exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y(2)O(3):Eu@SiO(2) concentration in vivo. With the pronounced X-RL for in-vivo imaging and dosimetry, it possesses significant potential for utilization as a precision theranostics producing highly efficient X-ray PDT for deep-seated tumors. Ivyspring International Publisher 2020-05-20 /pmc/articles/PMC7295068/ /pubmed/32550902 http://dx.doi.org/10.7150/thno.41752 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Chuang, Yao-Chen Chu, Chia-Hui Cheng, Shih-Hsun Liao, Lun-De Chu, Tsung-Sheng Chen, Nai-Tzu Paldino, Arthur Hsia, Yu Chen, Chin-Tu Lo, Leu-Wei Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
title | Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
title_full | Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
title_fullStr | Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
title_full_unstemmed | Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
title_short | Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
title_sort | annealing-modulated nanoscintillators for nonconventional x-ray activation of comprehensive photodynamic effects in deep cancer theranostics |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295068/ https://www.ncbi.nlm.nih.gov/pubmed/32550902 http://dx.doi.org/10.7150/thno.41752 |
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