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A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy |
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| Authors: | Daniel Boon Loong Teh Akshaya Bansal Chou Chai Tan Boon Toh Robert Alan Jappy Tucker Gil Gerald Lasam Gammad Yanzhuang Yeo Zhendong Lei Xiang Zheng Fengyuan Yang John S Ho Nagarjun Bolem Bing Cheng Wu Muthu Kumar Gnanasammandhan Lissa Hooi Gavin Stewart Dawe Camilo Libedinsky Wei-Yi Ong Barry Halliwell Edward Kai-Hua Chow Kah-Leong Lim Yong Zhang Brian K Kennedy |
| Affiliation: | 1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456 Singapore;2. Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583 Singapore;3. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456 Singapore
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232 Singapore;4. The N.1 Institute for Health, National University of Singapore, Singapore, 117599 Singapore;5. School of Biological Sciences, Nanyang Technological University, Singapore, 637551 Singapore;6. Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583 Singapore NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 117456 Singapore;7. Department of Electrical & Computer Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583 Singapore;8. The N.1 Institute for Health, National University of Singapore, Singapore, 117599 Singapore Department of Electrical & Computer Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583 Singapore;9. Division of Neurosurgery, National University Hospital, Singapore, 119228 Singapore;10. Department of Pathology, National University Hospital, Singapore, 119228 Singapore;11. Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599 Singapore;12. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600 Singapore;13. The N.1 Institute for Health, National University of Singapore, Singapore, 117599 Singapore Department of Psychology, Faculty of Arts and Social Sciences, National University of Singapore, Singapore, 117570 Singapore;14. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117594 Singapore;15. The N.1 Institute for Health, National University of Singapore, Singapore, 117599 Singapore Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599 Singapore Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600 Singapore;16. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456 Singapore |
| Abstract: | Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery. |
| Keywords: | hydrogels optical fibers photodynamic therapy upconversion wireless operation |