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

Abstract

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 (λem = 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 Cu2+‐mediated LDL oxidative aggregation via in situ formation of fluorophore‐bound Ox‐LDL in living cells. The red‐emissive probe Pro‐P1 (λem = 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

Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: a comprehensive review

“…Advances in fluorescence imaging are offering invaluable insights into key phenomena related to plaque progression [ 223 ]. A newly developed probe, Pro-P1, which is triggered by oxidized low-density lipoprotein, facilitates the direct observation of lipid oxidation and aggregation within live cells [ 224 ]. In the surgical context, the ability to visualize the full extent of atherosclerotic plaques during procedures has a significant impact on therapeutic outcomes.…”