Targeted High‐Resolution 3D Imaging of Tumor Vasculatures at Different Stages Using Far‐Red AIE Nanoparticles Compatible with Tissue Clearing

The occurrence and progression of blood vessels plays a pivotal role in different stages of tumor development, while current imaging techniques exhibit limited sensitivity to capture the dynamic changes of vasculature at different tumor stages. This drawback hinders the comprehensive understanding of the tumor microenvironment, thereby impeding the development of efficacious therapeutic strategies. Herein, a high-resolution three-dimensional (3D) imaging technology is developed for mapping and analyzing vasculatures at different tumor stages using HA@TANP, a supramolecular assembly of far-red fluorescence nanoparticles with aggregation-induced emission (AIE), compatible with tissue clearing. The hyaluronic acid (HA) in HA@TANP specifically targets CD44 antigen of tumor vasculature, while the acrylic acid in HA@TANP is applied for temperature-induced polymerization to ensure the covalent attachment of AIE fluorophores. Additionally, tissue optical clearing technology boosts light penetration and imaging resolution in dense tumor tissues. This strategy allows for the quantitative analyses of vascular diameter, length, and straightness and their correlation with various responses to treatments. The findings contribute to a more comprehensive understanding of distinct tumor vascular stages, providing valuable insights for enhanced cancer diagnosis and therapies from a tumor vascular-targeted perspective.