A two-photon fluorescence probe with endoplasmic reticulum targeting ability for turn-on sensing photosensitized singlet oxygen in living cells and brain tissues.

Endoplasmic reticulum (ER) is an indispensable organelle responsible for protein synthesis, transportation, and maintenance of Ca homeostasis in eukaryotic cells. Recent studies highlighted that ER-targeted photosensitizers with high yield of singlet oxygen (O) are effective in selectively disrupting ER function and are promising candidates for anticancer therapy. Unfortunately, no ER targetable fluorescent probes for determining O photosensitized in this photodynamic therapy process is available. In this work, we synthesized an ER-targetable, two-photon fluorescence probe, ER-O, for fluorescence turn-on sensing of O. ER-O demonstrated high sensitivity to O sensing with a wide detection range (0-2.75 μM) and a low detection limit (0.11 μM). ER-O also displayed excellent selectivity toward O out of other ROS and metal ions. Notably, ER-O exhibited low cytotoxicity but with specific ER targetable capability. On account of these advantageous features, fluctuations of O in living cells and brain tissues were effectively visualized by ER-O.