Fine-tuning J-aggregation <i>via</i> steric hindrance for high-efficiency NIR-II bioimaging and photothermal therapy

J-aggregates emitting in the second near-infrared window (NIR-II) show significant potential for <i>in vivo</i> imaging. However, progress has been hindered by the limited diversity of molecular scaffolds and the challenge of precisely controlling their aggregation. In this study, we employed a steric-hindrance strategy to design and synthesize a series of D-π-A molecules with tunable steric substituents, allowing for precise control of the J-aggregation process. The optimized molecule, FPy-1057, forms highly ordered J-aggregates as nanoparticles, demonstrating strong absorption at 1057 nm and bright emission at 1086 nm, with a photothermal conversion efficiency (PCE) of 71.2%. Leveraging these optical properties, FPy-1057 NPs enabled high-resolution imaging of fine vasculature, sentinel lymph node mapping, and surgical navigation of metastatic lesions. Additionally, FPy-1057 NPs exhibited potent photothermal therapy (PTT) efficacy, significantly inhibiting the growth of orthotopic tumors and metastasis to lymph nodes and lungs. Overall, this work introduces a strategy for the controlled construction of J-aggregates and offers valuable insights into the development of efficient NIR-II phototheranostic agents (PTAs) for advancing precision oncology.