Maximum Emission Peak Over 1500 nm of Organic Assembly for Blood–Brain Barrier‐Crossing NIR‐IIb Phototheranostics of Orthotopic Glioblastoma

Abstract The development of blood–brain barrier (BBB)‐crossing phototheranostic agents in second near‐infrared window (NIR‐II), especially in the range of 1500–1700 nm (NIR‐IIb), affords great opportunities for glioblastoma (GBM) management. Herein, an organic assembly (denoted as LET‐12) with the maximum absorption peak at 1400 nm and emission peak at 1512 nm with trailing over 1700 nm through the self‐assembly of organic small molecule IR‐1064 is designed and subsequently decorated with choline and acetylcholine analogs. The LET‐12 can effectively cross BBB through the brain's choline‐like receptors‐mediated transcytosis and accumulated in tumor tissues, thus achieving fluorescence/photoacoustic (FL/PA) duplex imaging of orthotopic GBM with ≈3.0 mm depth and a superior tumor‐to‐normal tissue signal ratio (20.93 ± 0.59 for FL imaging and 32.63 ± 1.16 for PA imaging, respectively). Owing to its good photothermal conversion ability, the LET‐12 also can serve as a photothermal conversion agent, achieving obvious tumor repression of orthotopic murine GBM model after once treatment. The findings indicate that the LET‐12 holds great potential for BBB‐crossing NIR‐IIb phototheranostics of orthotopic GBM. This self‐assembly strategy of organic small molecules opens a new avenue for the construction of NIR‐IIb phototheranostics.