Referential modification strategy based on phenolic hydroxyl-containing KSA luminogens for ER-targeting probe construction

Abstract

The endoplasmic reticulum (ER) plays essential roles in various physiological processes and is intimately connected to kinds of diseases. The development of ER-targeting theranostic agents is highly demanded for precise treatments, however, the effective and referential strategies for the construction of ER-targeting probes are limited. Herein, we developed series of ER-targeting luminogens based on keto-salicylaldehyde azine (KSA) framework by introducing phenolic hydroxyl group, which present good theranostic performance with selective enrichment in ER. Under systematical structure modulation, the key role of phenolic hydroxyl group at K-terminal in ER-targeting was experimentally confirmed. Besides, the cyanobenzyl moiety at S-terminal can enhance the luminous efficiency and improve cellular uptake ability. Moreover, the generated reactive oxygen species (ROS) of these KSA derivatives can efficiently trigger ER stress to induce the apoptosis of cancer cells, resulting in the effective inhibition of tumor cells both in vitro and in vivo. Therefore, this feasible modification strategy of inserting phenolic hydroxyl group to common multi-aryl-based luminogens provides a reliable and referential approach for ER-targeting probe establishment.

Keywords: Aggregation-induced emission; Endoplasmic reticulum targeting; Keto-salicylaldehyde azine; Phenolic hydroxyl; Photo-dynamic therapy.