Fine-tuning J-aggregation via 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 in vivo 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.