Maximum Emission Peak over 1500 nm of Organic Assembly for Blood-brain Barrier-crossing NIR-IIb Phototheranostics of Orthotopic Glioblastoma.

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, we designed 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 and subsequently decorated with choline and acetylcholine analogues. The LET-12 could 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 ratio (20.93 ± 0.59 for FL imaging and 32.63 ± 1.16 for PA imaging, respectively). Owing to its good light-heat conversion ability, the LET-12 also could serve as a photothermal conversion agent, achieving obvious tumor repression of orthotopic murine GBM model after once treatment. Our findings indicated 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. This article is protected by copyright. All rights reserved.