1. Organelle-Specific Thiochromenocarbazole Imide Derivative as a Heavy-Atom-Free Type I Photosensitizer for Biomolecule-Triggered Image-Guided Photodynamic Therapy.
- Author
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Saczuk K, Kassem A, Dudek M, Sánchez DP, Khrouz L, Allain M, Welch GC, Sabouri N, Monnereau C, Josse P, Cabanetos C, and Deiana M
- Subjects
- Humans, Mitochondria drug effects, Mitochondria metabolism, Singlet Oxygen metabolism, Singlet Oxygen chemistry, HeLa Cells, Light, Cell Survival drug effects, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Photochemotherapy, Carbazoles chemistry, Carbazoles pharmacology
- Abstract
Modern photodynamic therapy (PDT) demands next-generation photosensitizers (PSs) that overcome heavy-atom dependency and enhance efficacy beyond traditional, highly oxygen-dependent type II mechanisms. We introduce herein TCI-NH , as a thiochromenocarbazole imide derivative designed for type I photodynamic action. Upon light activation, TCI-NH efficiently favors superoxide (O
2 •- ) and PS-centered radical formation instead of singlet oxygen (1 O2 ) generation. Its high luminescence efficiency and selective localization in both the endoplasmic reticulum and mitochondria enable precise, image-guided PDT. Notably, interactions with biomolecules, such as serum albumin or DNA, enhance TCI-NH 's emission by up to 40-fold and amplify radical generation by up to 5-fold. With negligible dark toxicity, this results in ∼120 nM photocytotoxicity along with an impressive phototherapeutic index exceeding 200. Real-time live-cell imaging revealed rapid, light-triggered cytotoxicity characterized by apoptotic body formation and extensive cellular damage. With its small size, heavy-atom-free structure, exceptional, organelle specificity, and therapeutic efficacy, TCI-NH sets a new benchmark for anticancer type I PDT.- Published
- 2025
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