Conditional Singlet Oxygen Generation through a Bioorthogonal DNA‐targeted Tetrazine Reaction |
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Authors: | Greta Linden,Lei Zhang,Fabian Pieck,Uwe Linne,Dmitri Kosenkov,Ralf Tonner,Olalla V zquez |
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Affiliation: | Greta Linden,Lei Zhang,Fabian Pieck,Uwe Linne,Dmitri Kosenkov,Ralf Tonner,Olalla Vázquez |
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Abstract: | We report the use of bioorthogonal reactions as an original strategy in photodynamic therapy to achieve conditional phototoxicity and specific subcellular localization simultaneously. Our novel halogenated BODIPY‐tetrazine probes only become efficient photosensitizers (ΦΔ≈0.50) through an intracellular inverse‐electron‐demand Diels–Alder reaction with a suitable dienophile. Ab initio computations reveal an activation‐dependent change in decay channels that controls 1O2 generation. Our bioorthogonal approach also enables spatial control. As a proof‐of‐concept, we demonstrate the feasibility of the selective activation of our dormant photosensitizer in cellular nuclei, causing cancer cell death upon irradiation. Thus, our dual biorthogonal, activatable photosensitizers open new venues to combat current limitations of photodynamic therapy. |
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Keywords: | bioorthogonal reactions BODIPY dyes photodynamic therapy singlet oxygen tetrazine |
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