All-natural-molecule, bioluminescent photodynamic therapy results in complete tumor regression and prevents metastasis

Self-luminescent photodynamic therapy (PDT) has gained attention owing to its potential to enable effective phototherapy without the bottleneck of shallow light penetration into tissues. However, the biosafety concerns and low cytotoxic effect of self-luminescent reagents in vivo have been problems....

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Bibliographic Details
Published in:Biomaterials 2023-05, Vol.296, p.122079-122079, Article 122079
Main Authors: Yan, Hao, Forward, Sarah, Kim, Kwon-Hyeon, Wu, Yue, Hui, Jie, Kashiparekh, Anokhi, Yun, Seok-Hyun
Format: Article
Language:English
Subjects:
Animals
Bioluminescence
Biophotonics
Breast cancer
Cell Line, Tumor
Luminescence
Mice
Neoplasms - drug therapy
Photochemotherapy - methods
Photomedicine
Photosensitizing Agents - therapeutic use
Phototherapy
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Summary:Self-luminescent photodynamic therapy (PDT) has gained attention owing to its potential to enable effective phototherapy without the bottleneck of shallow light penetration into tissues. However, the biosafety concerns and low cytotoxic effect of self-luminescent reagents in vivo have been problems. Here, we demonstrate efficacious bioluminescence (BL)-PDT by using bioluminescence resonance energy transfer (BRET) conjugates of a clinically approved photosensitizer, Chlorin e6, and a luciferase, Renilla reniformis; both derived from biocompatible, natural molecules. With over 80% biophoton utilization efficiency and membrane-fusion liposome-assisted intracellular delivery, these conjugates produce effective, targeted cancer cell killing. Specifically, in an orthotopic mouse model of 4T1 triple-negative breast cancer, BL-PDT showed strong therapeutic effects on large primary tumors and a neoadjuvant outcome in invasive tumors. Furthermore, BL-PDT resulted in complete tumor remission and prevention of metastasis for early-stage tumors. Our results demonstrate the promise of molecularly-activated, clinically viable, depth-unlimited phototherapy.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2023.122079