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

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.