Metal‐Free Far‐Red Light‐Driven Photolysis via Triplet Fusion to Enhance Checkpoint Blockade Immunotherapy

Metal‐free long‐wavelength light‐driven prodrug photoactivation is highly desirable for applications such as neuromodulation, drug delivery, and cancer therapy. Herein, via triplet fusion, we report on the far‐red light‐driven photo‐release of an anti‐cancer drug by coupling the boron‐dipyrromethene...

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Published in:Angewandte Chemie International Edition 2023-03, Vol.62 (11), p.e202218341-n/a
Main Authors: Zeng, Le, Jiang, Lin‐Han, Li, Jia‐Yao, Huang, Ling, Chen, Yongzhi, Yu, Nuo, Wang, Lei, Huang, Kai, Peng, Jing, Han, Gang
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents
BODIPY
Boron
Cancer
Dioxygenase
Drug delivery
Immune Checkpoint Inhibitors
Immunotherapy
Indoleamine-Pyrrole 2,3,-Dioxygenase
Light
Metals
Mice
Nanoparticles
Neuromodulation
Photoactivation
Photolysis
Triplet Fusion
Tumor Immunotherapy
Tumors
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Summary:Metal‐free long‐wavelength light‐driven prodrug photoactivation is highly desirable for applications such as neuromodulation, drug delivery, and cancer therapy. Herein, via triplet fusion, we report on the far‐red light‐driven photo‐release of an anti‐cancer drug by coupling the boron‐dipyrromethene (BODIPY)‐based photosensitizer with a photocleavable perylene‐based anti‐cancer drug. Notably, this metal‐free triplet fusion photolysis (TFP) strategy can be further advanced by incorporating an additional functional dopant, i.e. an immunotherapy medicine inhibiting the indoleamine 2,3‐dioxygenase (IDO), with the far‐red responsive triplet fusion pair in an air‐stable nanoparticle. With this IDO inhibitor‐assisted TFP system we observed efficient inhibition of primary and distant tumors in a mouse model at record‐low excitation power, compared to other photo‐assisted immunotherapy approaches. This metal‐free TFP strategy will spur advancement in photonics and biophotonics fields. A metal‐free triplet fusion photolysis (TFP) system, consisting of a BODIPY photosensitizer and a perylene prodrug (PyCl), released an anti‐cancer drug upon far‐red light irradiation. Encapsulation of this TFP system and a 2,3‐dioxygenase (IDO) inhibitor within a nanoparticle enabled far‐red light‐promoted checkpoint blockade immunotherapy for effective inhibition of both local and metastatic tumors under extremely low excitation (20 mW cm−2).
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202218341