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

• Published in: Theranostics 2020-01, Vol.10 (15), p.6758-6773
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Annealing; Cancer therapies; Cell Line, Tumor; Efficiency; Energy; Ethanol; Female; Hypoxia; Light; Mice; Mice, Nude; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - radiation effects; Nanotechnology - instrumentation; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Photochemotherapy - instrumentation; Photochemotherapy - methods; Photosensitizing Agents - administration & dosage; Radiation therapy; Research Paper; Silicon Dioxide - chemistry; Singlet Oxygen; Theranostic Nanomedicine; Tumors; X-Rays; Xenograft Model Antitumor Assays; Yttrium - chemistry
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.41752

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 O :Eu@SiO ) with an annealing process. Our results revealed that annealed Y O :Eu@SiO could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y O :Eu@SiO was demonstrated to enable the generation of electron-hole (e -h ) pairs in Y O under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y O :Eu@SiO with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation ( O ) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y O :Eu@SiO , achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y O :Eu@SiO exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y O :Eu@SiO concentration . With the pronounced X-RL for imaging and dosimetry, it possesses significant potential for utilization as a precision theranostics producing highly efficient X-ray PDT for deep-seated tumors.