Theranostics 2020; 10(15):6758-6773. doi:10.7150/thno.41752 This issue Cite

Research Paper

Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics

Yao-Chen Chuang1*, Chia-Hui Chu1*, Shih-Hsun Cheng1,2, Lun-De Liao1, Tsung-Sheng Chu1, Nai-Tzu Chen3, Arthur Paldino4, Yu Hsia1, Chin-Tu Chen2, Leu-Wei Lo1✉

1. Institute of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan.
2. Department of Radiology, The University of Chicago, Chicago, IL 60637, USA.
3. Department of Cosmeceutics, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan 40402.
4. Faculté de médecine Lyon-Est, Université Claude Bernard, 8 Avenue Rockefeller, Lyon 69008, France.
*These authors contributed equally to this work.

Citation:
Chuang YC, Chu CH, Cheng SH, Liao LD, Chu TS, Chen NT, Paldino A, Hsia Y, Chen CT, Lo LW. Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics. Theranostics 2020; 10(15):6758-6773. doi:10.7150/thno.41752. https://www.thno.org/v10p6758.htm
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Abstract

Graphic abstract

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 (Y2O3:Eu@SiO2) with an annealing process. Our results revealed that annealed Y2O3:Eu@SiO2 could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y2O3:Eu@SiO2 was demonstrated to enable the generation of electron-hole (e--h+) pairs in Y2O3 under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y2O3:Eu@SiO2 with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation (SO2) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y2O3:Eu@SiO2, achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y2O3:Eu@SiO2 exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y2O3:Eu@SiO2 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.

Keywords: Photodynamic therapy, annealing, nanoscintillator, fractionated radiotherapy, X-ray induced radioluminescence, vascular remodeling, radioresistance


Citation styles

APA
Chuang, Y.C., Chu, C.H., Cheng, S.H., Liao, L.D., Chu, T.S., Chen, N.T., Paldino, A., Hsia, Y., Chen, C.T., Lo, L.W. (2020). Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics. Theranostics, 10(15), 6758-6773. https://doi.org/10.7150/thno.41752.

ACS
Chuang, Y.C.; Chu, C.H.; Cheng, S.H.; Liao, L.D.; Chu, T.S.; Chen, N.T.; Paldino, A.; Hsia, Y.; Chen, C.T.; Lo, L.W. Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics. Theranostics 2020, 10 (15), 6758-6773. DOI: 10.7150/thno.41752.

NLM
Chuang YC, Chu CH, Cheng SH, Liao LD, Chu TS, Chen NT, Paldino A, Hsia Y, Chen CT, Lo LW. Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics. Theranostics 2020; 10(15):6758-6773. doi:10.7150/thno.41752. https://www.thno.org/v10p6758.htm

CSE
Chuang YC, Chu CH, Cheng SH, Liao LD, Chu TS, Chen NT, Paldino A, Hsia Y, Chen CT, Lo LW. 2020. Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics. Theranostics. 10(15):6758-6773.

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