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

Abstract

Endoplasmic reticulum (ER) is an indispensable organelle responsible for protein synthesis, transportation, and maintenance of Ca²⁺ homeostasis in eukaryotic cells. Recent studies highlighted that ER-targeted photosensitizers with high yield of singlet oxygen (¹O₂) are effective in selectively disrupting ER function and are promising candidates for anticancer therapy. Unfortunately, no ER targetable fluorescent probes for determining ¹O₂ photosensitized in this photodynamic therapy process is available. In this work, we synthesized an ER-targetable, two-photon fluorescence probe, ER-¹O₂, for fluorescence turn-on sensing of ¹O₂. ER-¹O₂ demonstrated high sensitivity to ¹O₂ sensing with a wide detection range (0-2.75 μM) and a low detection limit (0.11 μM). ER-¹O₂ also displayed excellent selectivity toward ¹O₂ out of other ROS and metal ions. Notably, ER-¹O₂ exhibited low cytotoxicity but with specific ER targetable capability. On account of these advantageous features, fluctuations of ¹O₂ in living cells and brain tissues were effectively visualized by ER-¹O₂.

Keywords: Endoplasmic reticulum; Singlet oxygen; Tissues; Turn-on; Two-photon fluorescence.