Two-photon uncaging of bioactive compounds: Starter guide to an efficient IR light switch

Maxime Klausen, Mireille Blanchard-Desce

Research output: Contribution to journalArticlepeer-review


Triggering physiological responses with a light switch has become a reality with the development of smart molecular probes such as photolabile protecting groups (PPGs), able to “uncage” biological ligands on demand. To make the light switch virtually harmless and confine the excitation to the single-cell level, the caged ligands can be released using two-photon (2 P) absorption and 2 P microscopy using red/infrared light. This exceptional level of precision however comes at the cost of a reduced photosensitivity and a poor compatibility of early PPGs with 2 P excitation. This review aims to provide a tutorial guidebook to the design of 2 P-sensitive PPGs suitable for optobiology by discussing challenges, strategies and progress in uncaging of bioactive compounds. To do so, we first recall the photo-physical principles governing 2 P absorption, and the resulting ground rules in the design of efficient 2 P absorbing organic dyes. We then detail how following these guidelines has led to tremendous progress in the development of a new generation of caged compounds, and the implications in the fields of biophotonics, from neurology to targeted therapy.
Original languageEnglish
Article number100423
JournalJournal of Photochemistry and Photobiology C: Photochemistry Reviews
Early online date31 May 2021
Publication statusE-pub ahead of print - 31 May 2021


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