High Performance Aggregation-Induced Emission Nanoprobes for Image-Guided Cancer Surgery
Received date: 2020-10-31
Online published: 2021-01-05
Supported by
National Natural Science Foundation of China(51961160730); National Natural Science Foundation of China(51873092); National Natural Science Foundation of China(81921004); National Key R&D Program of China(Intergovernmental Cooperation Project)(2017YFE0132200); and the Tianjin Science Fund for Distinguished Young Scholars(19JCJQJC61200)
Far red/near infrared (FR/NIR) materials have attracted wide attention due to their great potential in various applications, particularly in bio-imaging. However, it is still a challenge to manufacture organic FR/NIR materials with quite high efficiency and long emission wavelength, owing to the dominance of non-radiative deactivation in the dissipation of absorbed light excitation energy when the electronic bandgap decreases. Herein, a series of donor-acceptor-donor (D-A-D) type compounds based on benzoselenidazole are developed through the regulation of molecular aggregation states by twisted conformation groups. In one hand, the compound TPE-DPA-Se (tetraphenylethylene-diphenylamine-benzoselenidazole) exhibits the best aggregation-induced emission (AIE) properties among these compounds. In another hand, the obtained TPE-DPA-Se showed over 150 nm Stokes shift, which can be used to avoid the interference between excitation and emission light, as well as the near-infrared emission spectrum away from the organism auto-fluorescence, which was beneficial for the bio-application. Next, density functional theory (DFT) calculation was carried out with Gaussian 09W program at B3LYP/6-31G** level to determine the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) distributions and the optimized structures of these compounds. Then TPE-DPA-Se was formulated into nanoparticles by nanoprecipitation method with an amphiphilic co-polymer 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (MPEG2000-DSPE) as the doping matrix. TPE-DPA-Se exhibited excellent aqueous diameter stability in nanoparticle-state, as well as impressive luminescence in aqueous system with higher efficiency of up to 16.48%, which are suitable for many fields. To evaluate the biocompatibility of the TPE-DPA-Se NPs, we further carried out 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay. The result indicated their negligible toxicity. Encouraged by the excellent performance of these luminogens in nanoparticle state, a successful 4T1 cells imaging was demonstrated. Next, to set up the tumor-bearing mouse model, the luciferase-expressed 4T1 cancer cells were injected into the healthy mice via intraperitoneal injection. After about 7 days, the abdominal metastatic tumors were formed with many nodules in the abdominal cavity. The fluorescent image can merged with bioluminescence image completely and image-guided tumor resection is verified in this work, particularly for the micro-sized tumor of intraoperative detection.
Heqi Gao , Di Jiao , Hanlin Ou , Jingtian Zhang , Dan Ding . High Performance Aggregation-Induced Emission Nanoprobes for Image-Guided Cancer Surgery[J]. Acta Chimica Sinica, 2021 , 79(3) : 319 -325 . DOI: 10.6023/A20100501
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