Li_2025_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_347_126899

Hepatic carcinoma is one of the most common malignancies with low survival rates due to insufficient therapeutics while early detection of hepatic tumors remains key to reducing mortality of liver cancer. However, current clinical methods are hard to detect pathological changes in early-stage cases while the detection rate of liquid biopsy-based assay is limited. Thus, effective tools for accurate and sensitive detection of hepatic tumors are still in urgent need. To date, fluorescent probes targeting cancer-related biomarkers and cellular environments have attracted intense attention, among which "dual-locked" probes have developed to avoid false-positives and have shown great potential in accurate detection of tumors. Herein, carboxylesterase (CE), a widely expressed serine hydrolase that shows high relevance with hepatic carcinoma progression and tumor-associated cellular viscosity were chosen as co-targets for hepatic tumor targeting probe development. By rational design and construction of a "dual-locked" probe for simultaneously sensing carboxylesterase activity and cellular viscosity, the newly acquired probe DCI-CV displayed high specificity and sensitivity toward CE in both in vitro assays and cell imaging. Most importantly, DCI-CV was successfully applied to imaging subcutaneous and orthotopic transplanted hepatic tumors with high specificity, demonstrating DCI-CV as a potential tool in hepatic tumor detection and related surgical navigation.