Oxidized Low-Density Lipoprotein (Ox-LDL)-Triggered Double-Lock Probe for Spatiotemporal Lipoprotein Oxidation and Atherosclerotic Plaque Imaging.

Low-density lipoprotein (LDL), especially oxidative modified LDL (Ox-LDL), is the key risk factor for plaque accumulation and the development of cardiovascular disease (CVDs). Herein,  we develop a highly specific Ox-LDL-triggered fluorogenic-colorimetric probe Pro-P1 for visualizing the oxidation and aggregation progress of lipoproteins and plaque. A series of donor-acceptor modified green fluorescent protein chromophore (GFP) containing carbazole as an electron donor and pyridine-vinyl (P1), phenol-vinyl (P2), N, N-dimethylaniline-vinyl (P3), thiophene-vinyl (P4) substituent, respectively, have been synthesized and evaluated. Emission spectroscopy and theoretical calculations of P1-P4 indicate that P1 shows enhanced green fluorescence (λ em = 560 nm) by inhibiting its twisted intramolecular charge transfer (TICT) in the presence of Ox-LDL. This feature allows us to select P1 as a selective probe to directly visualize ferroptosis and Cu 2+ -mediated LDL oxidative aggregation via in situ formation of fluorophore-bound Ox-LDL in living cells. The red-emissive probe Pro-P1 (λ em = 660 nm)  was prepared via borate protection of P1, which can be cleaved into P1 under high expression of HOCl and Ox-LDL condition at the lesion site, resulting in enhanced green emission. The plaque area and size with clear boundaries can be delineated by colorimetric fluorescence imaging and fluorescence lifetime imaging (FLIM) with precise differentiation. This article is protected by copyright. All rights reserved.