Novel far-red fluorescent theranostic probes for selective imaging and targeted therapy of BET proteins in breast cancer.

BET family proteins, which regulate disease-related gene expression by coupling chromatin states with transcriptional regulation through recognition of histone acetylation signals, have emerged as critical drug targets in various cancers. Therefore, real-time monitoring of BET protein activity in tumor cells, tissues, and living organisms is of great significance for inhibitor development and related research. Based on our previous work, a series of far-red fluorescent probes targeting the BET family proteins were designed and synthesized, with the aim of establishing a theranostic system that can be applied at both the cellular and tissue levels. Among these probes, L3 exhibited good binding affinity for BET family proteins and demonstrated outstanding performance in tracking target proteins at both cellular and tissue levels. Significantly, L3 facilitated selective imaging of BRD2/3/4 proteins with a clear distinction between malignant and healthy tissues, while also displaying potent in vitro anticancer activity comparable to JQ1(+), by regulating cell cycle- and apoptosis-associated genes. Furthermore, in vivo imaging studies confirmed the potential of this agent for fluorescence-directed tumor excision surgery. Such results position L3 as a multifunctional chemical tool that integrates real-time visualization with therapeutic efficacy for application in breast cancer investigation.