Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators
Non-invasive phototherapy has been emerging as an ambitious tactic for suppression of amyloid-β (Aβ) self-assembly against Alzheimer's disease (AD). However, it remains a daunting challenge to develop efficient photosensitizers for Aβ oxygenation that are activatable in a deep brain tissue thro...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/170549 |
| _version_ | 1826117178271727616 |
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| author | Ma, Mengmeng Wang, Jing Jiang, Hao Chen, Qiushui Xiao, Yi Yang, Huanghao Lin, Li |
| author2 | Institute for Digital Molecular Analytics and Science (IDMxS) |
| author_facet | Institute for Digital Molecular Analytics and Science (IDMxS) Ma, Mengmeng Wang, Jing Jiang, Hao Chen, Qiushui Xiao, Yi Yang, Huanghao Lin, Li |
| author_sort | Ma, Mengmeng |
| collection | NTU |
| description | Non-invasive phototherapy has been emerging as an ambitious tactic for suppression of amyloid-β (Aβ) self-assembly against Alzheimer's disease (AD). However, it remains a daunting challenge to develop efficient photosensitizers for Aβ oxygenation that are activatable in a deep brain tissue through the scalp and skull, while reducing side effects on normal tissues. Here, we report an Aβ targeted, low-dose X-ray-excitable long-afterglow scintillator (ScNPs@RB/Ab) for efficient deep-brain phototherapy. We demonstrate that the as-synthesized ScNPs@RB/Ab is capable of converting X-rays into visible light to activate the photosensitizers of rose bengal (RB) for Aβ oxygenation through the scalp and skull. We show that the ScNPs@RB/Ab persistently emitting visible luminescence can substantially minimize the risk of excessive X-ray exposure dosage. Importantly, peptide KLVFFAED-functionalized ScNPs@RB/Ab shows a blood-brain barrier permeability. In vivo experimental results validated that ScNPs@RB/Ab alleviated Aβ burden and slowed cognitive decline in triple-transgenic AD model mice at extremely low X-ray doses without side effects. Our study paves a new pathway to develop high-efficiency transcranial AD phototherapy. STATEMENT OF SIGNIFICANCE: Non-invasive phototherapy has been emerging as an ambitious tactic for suppression of amyloid-β (Aβ) self-assembly against Alzheimer's disease (AD). However, it remains a daunting challenge to develop efficient photosensitizers for Aβ oxygenation that are activatable in a deep brain tissue through the scalp and skull, while reducing side effects on normal tissues. Herein, we report an Aβ targeted, low-dose X-ray-excitable long-afterglow scintillators (ScNPs@RB/Ab) for efficient deep-brain phototherapy. In vivo experimental results validated that ScNPs@RB/Ab alleviated Aβ burden and slowed cognitive decline in triple-transgenic AD model mice at extremely low X-ray doses without side effects. |
| first_indexed | 2024-10-01T04:23:23Z |
| format | Journal Article |
| id | ntu-10356/170549 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:23:23Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1705492023-09-19T02:55:32Z Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators Ma, Mengmeng Wang, Jing Jiang, Hao Chen, Qiushui Xiao, Yi Yang, Huanghao Lin, Li Institute for Digital Molecular Analytics and Science (IDMxS) Engineering::Materials Scintillator X-ray Non-invasive phototherapy has been emerging as an ambitious tactic for suppression of amyloid-β (Aβ) self-assembly against Alzheimer's disease (AD). However, it remains a daunting challenge to develop efficient photosensitizers for Aβ oxygenation that are activatable in a deep brain tissue through the scalp and skull, while reducing side effects on normal tissues. Here, we report an Aβ targeted, low-dose X-ray-excitable long-afterglow scintillator (ScNPs@RB/Ab) for efficient deep-brain phototherapy. We demonstrate that the as-synthesized ScNPs@RB/Ab is capable of converting X-rays into visible light to activate the photosensitizers of rose bengal (RB) for Aβ oxygenation through the scalp and skull. We show that the ScNPs@RB/Ab persistently emitting visible luminescence can substantially minimize the risk of excessive X-ray exposure dosage. Importantly, peptide KLVFFAED-functionalized ScNPs@RB/Ab shows a blood-brain barrier permeability. In vivo experimental results validated that ScNPs@RB/Ab alleviated Aβ burden and slowed cognitive decline in triple-transgenic AD model mice at extremely low X-ray doses without side effects. Our study paves a new pathway to develop high-efficiency transcranial AD phototherapy. STATEMENT OF SIGNIFICANCE: Non-invasive phototherapy has been emerging as an ambitious tactic for suppression of amyloid-β (Aβ) self-assembly against Alzheimer's disease (AD). However, it remains a daunting challenge to develop efficient photosensitizers for Aβ oxygenation that are activatable in a deep brain tissue through the scalp and skull, while reducing side effects on normal tissues. Herein, we report an Aβ targeted, low-dose X-ray-excitable long-afterglow scintillators (ScNPs@RB/Ab) for efficient deep-brain phototherapy. In vivo experimental results validated that ScNPs@RB/Ab alleviated Aβ burden and slowed cognitive decline in triple-transgenic AD model mice at extremely low X-ray doses without side effects. 2023-09-19T02:55:31Z 2023-09-19T02:55:31Z 2023 Journal Article Ma, M., Wang, J., Jiang, H., Chen, Q., Xiao, Y., Yang, H. & Lin, L. (2023). Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators. Acta Biomaterialia, 155, 635-643. https://dx.doi.org/10.1016/j.actbio.2022.10.049 1742-7061 https://hdl.handle.net/10356/170549 10.1016/j.actbio.2022.10.049 36328129 2-s2.0-85141964692 155 635 643 en Acta Biomaterialia © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. |
| spellingShingle | Engineering::Materials Scintillator X-ray Ma, Mengmeng Wang, Jing Jiang, Hao Chen, Qiushui Xiao, Yi Yang, Huanghao Lin, Li Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators |
| title | Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators |
| title_full | Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators |
| title_fullStr | Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators |
| title_full_unstemmed | Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators |
| title_short | Transcranial deep-tissue phototherapy for Alzheimer's disease using low-dose X-ray-activated long-afterglow scintillators |
| title_sort | transcranial deep tissue phototherapy for alzheimer s disease using low dose x ray activated long afterglow scintillators |
| topic | Engineering::Materials Scintillator X-ray |
| url | https://hdl.handle.net/10356/170549 |
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