A mitochondria-targeting NIR ratiometric fluorescent probe for visualizing the dynamics of vicinal dithiol-containing proteinsin a psoriasis mouse model.

Abstract

BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of inflammatory cells, epidermal hypertrophy, aberrant keratinocyte proliferation, and desquamation, which collectively lead to severe impairment of patients' quality of life. This pathological milieu is closely linked to oxidative stress, which has emerged as a crucial contributor to its progression. Within this context, systemic profiling of vicinal dithiol-containing proteins (VDPs), serving as critical modulator of protein conformation, cellular redox balance, and diverse physiological processes may provide valuable insights into the molecular mechanisms underlying psoriasis and its complex biological networks. RESULTS: Herein, we report the rational construction of a near-infrared (NIR) ratiometric fluorescent probe (MCQ-4) for the precise detection of VDPs in living environment. MCQ-4 utilized a quinoline conjugated coumarin-based luminophore connected with N-benzyl-methacrylamide-based VDPs receptor unit. Upon treating with reduced bovine serum albumin (rBSA), MCQ-4 exhibited a rapid, ratiometric and colorimetric fluorescence (584 nm/735 nm) response, demonstrating reputable selectivity and sensitivity, and high biocompatibility. Furthermore, MCQ-4 enabled dual-emission imaging of endogenous VDPs in living HepG2 and HeLa cells, with excellent mitochondrial localization potential (PC = 0.95). Notably, this study reveals the first evidence of a significant depletion of reduced VDPs in psoriasis mice model, highlighting the potential of MCQ-4 as a powerful tool for studying the pathophysiology of psoriasis. SIGNIFICANCE: This study pioneers the precise profiling of VDPs alterations during psoriasis for the comprehensive elucidation of redox dysregulation and its contribution to disease progression. Additionally, the findings of this work establish MCQ-4 as a promising tool for advancing mechanistic studies of psoriasis and its biological pathways.