Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China.
Adv Mater. 2023 Jun;35(22):e2208097. doi: 10.1002/adma.202208097. Epub 2023 Apr 7.
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.
血脑屏障（BBB）穿越光热治疗剂在第二近红外窗口（NIR-II），特别是在 1500-1700nm（NIR-IIb）范围内的发展，为胶质母细胞瘤（GBM）的治疗提供了巨大的机会。在此，通过有机小分子 IR-1064 的自组装设计了一种具有最大吸收峰在 1400nm 和发射峰在 1512nm 的有机组装体（表示为 LET-12），并通过进一步修饰胆碱和乙酰胆碱类似物来延长其拖尾至 1700nm 以上。LET-12 可以通过大脑的胆碱样受体介导的转胞吞作用有效地穿越 BBB，并在肿瘤组织中积累，从而实现了对原位 GBM 的荧光/光声（FL/PA）双模式成像，深度约为 3.0mm，肿瘤与正常组织的信号比（FL 成像为 20.93±0.59，PA 成像为 32.63±1.16）非常高。由于其良好的光热转换能力，LET-12 还可以作为光热转换剂，在一次治疗后实现了原位小鼠 GBM 模型的明显肿瘤抑制。研究结果表明，LET-12 具有作为 BBB 穿越 NIR-IIb 光热治疗剂治疗原位 GBM 的巨大潜力。这种有机小分子的自组装策略为构建 NIR-IIb 光热治疗剂开辟了新途径。
