Engineered Oligomeric Indolizine-Fused BODIPY Fluorophores for Interventional NIR-II Fluorescence Imaging of Acute Cardio-Cerebrovascular Events.

Abstract

Vascular networks are essential for life maintenance, and their dysfunction can result in severe diseases. However, current biomedical imaging modalities possess constraints in diagnosing these diseases. NIR-II fluorescence imaging has emerged as a powerful tool, offering rapid feedback, high spatial resolution, and superior biosafety. Among NIR-II fluorophores, BODIPY oligomers stand out due to their excellent optical performance and versatile tunability. Yet, they confront challenges in design, synthesis, brightness, and blood circulation half-life. Here, we introduce a novel approach that integrates vascular interventional techniques with NIR-II fluorescence imaging, utilizing de-novo designed and synthesized indolizine-fused BODIPY oligomers for diagnosing cardio-cerebrovascular diseases. The synthesized oligomers absorb and emit within the NIR-II window. Notably, (ααSIFB)₄, a representative singly indolizine-fused tetramer, features highly planar indolizine-fused BODIPY subunits with a twisted linkage, mitigating detrimental aggregation via suppressed intermolecular π-π interactions. Consequently, (ααSIFB)₄ demonstrates high brightness, a substantial Stokes shift, and robust chemical and photostability. ((ααSIFB)₄@PSMA) exhibits remarkable performance in imaging mouse cardio-cerebral vasculature. Crucially, direct administration via a interventional catheter addresses the issue of short blood circulation half-life, significantly enhancing target-site contrast. Interventional NIR-II imaging with (ααSIFB)₄@PSMA enables real-time, continuous monitoring of vascular dynamics and visualization of acute cardio-cerebrovascular events.