Anti-Scarring Drug Screening with Near-Infrared Molecular Probes Targeting Fibroblast Activation Protein-α

Abnormal scarring is a hyper-proliferative wound healing disorder, which causes itch, pain, psychological distress, and even limiting limb mobility. Unfortunately, no satisfactory treatment exists to date. Drug screening identifies suitable drugs or drug combinations that inhibit abnormal scarring from a large selection of candidates. However, current techniques are often laborious and technically complex. Herein, we adopt a near-infrared fluorescence probe (FNP1) for fibroblast activation protein (FAP)α, a biomarker overexpressed in skin fibroblasts derived from abnormal scars, to rapidly assess (<30 min) drug candidates for the treatment. FNP1 has high sensitivity, even detecting FAPα up-regulation with as little as 0.016 ng/mL TGFβ1, 125-fold lower than typical culture concentrations. The identified drug candidates (RepSox and Thiazovivin) show similar potent anti-scarring activity as the existing anti-scarring compounds and further suppress the expression of other scar biomarkers including connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and collagen type 1 (COL1A1).