A dual-responsive fluorescent probe for 4-methylbenzenethiol detection and viscosity imaging of pathological processes.
Abstract
4-Methylbenzenethiol (MTP), a reactive thiol compound widely utilized in the production of pesticides, polymers, and pharmaceuticals, poses potential risks to biological systems owing to its high toxicity. Meanwhile, viscosity, an important physicochemical parameter of the cellular microenvironment, is significantly altered under pathological conditions, including inflammation, fibrosis, and tumors, due to extracellular matrix remodeling and increased cellular crowding. Therefore, the development of fluorescent sensors capable of simultaneously monitoring MTP and viscosity is highly desirable for understanding complex biological processes. Herein, two small-molecule fluorescent probes, Lcy-MTP-1 and Lcy-MTP-2, were constructed by integrating a benzoindole-based hemicyanine fluorophore with a 2,4-dinitrodiphenyl ether recognition unit through carbon‑carbon double bonds with different conjugation lengths. Lcy-MTP-1 enabled ratiometric detection of MTP in solution through thiophenol-triggered cleavage of the recognition moiety and exhibited a rapid response (<5 min), high sensitivity (limit of detection, LOD = 0.77 μM), broad pH tolerance, and excellent anti-interference capability. In addition, Lcy-MTP-1 showed an 11-fold fluorescence enhancement in response to viscosity changes ranging from 0.7 to 687.5 cP. Biological studies revealed that both probes possess favorable metabolic clearance properties. Notably, Lcy-MTP-1 successfully enabled in vivo visualization of pathological alterations and clearly discriminated diseased tissues from normal tissues in inflammation, tumor, and non-alcoholic steatohepatitis (NASH) models. These results establish Lcy-MTP-1 as a versatile dual-responsive fluorescent sensor for correlating chemical and microenvironmental changes in living systems, providing a promising platform for viscosity-associated disease monitoring.
Abstract as supplied by the indexing source. © the authors / publisher.