# Double Disguise: Camouflaging Photocages for Bioorthogonally Controlled Conditional Activation

## TL;DR

This paper introduces a new method to control photocage activation using a camouflaging strategy that requires both light and a bioorthogonal reagent.

## Contribution

A novel substitution-based approach to create inactive, colorless photocages that can be selectively reactivated using bioorthogonal chemistry.

## Key findings

- Camouflaged photocages based on aminofluorone are colorless and inactive until bioorthogonally reactivated.
- The method was successfully demonstrated in cells using a topoisomerase inhibitor, SN38.
- This approach adds an extra layer of control to photoassisted delivery systems.

## Abstract

Photocages provide
excellent spatiotemporal control over biological
processes; however, strategies to restrict their activation to specific
conditions remain limited. In this work, we demonstrate that our recently
introduced photocages based on the aminofluorone (rhodol) choromophore
can be rendered completely inactive through a single substitution
on the oxygen auxochrome. These ‘camouflaged’ photocages
are entirely colorless, preventing photouncaging in their disabled
state. Bioorthogonal removal of the camouflaging group restores the
photoactivity of the cages, introducing an additional layer of control
for photoassisted delivery systems. We further demonstrate this concept
of substitution-dependent, bioorthogonally regulated photoactivation
in a cellular context, where both a bioorthogonal reagent and light
were required to release a potent topoisomerase inhibitor, SN38.