Design And Synthesize Aggregation-induced Emission(AIE) Fluorophores For In Vivo NIR-Ⅱ Imaging

Molecular imaging is a highly comprehensive subject,including Optical imaging(OI),Magnetic Resonance Imaging(MRI)and so on.OI has been widely exploited in biomedical imaging due to its high spatial and temporal resolution,biocompatibility,real-time imaging,easy-operation,low cost and other advantages.In OI,Near-infrared Ⅱ(NIR-Ⅱ)fluorescence imaging holds great promise for in vivo imaging and imaging-guided surgery with deep penetration and high spatiotemporal resolution.The most important factor counts for the performance of NIR-Ⅱ fluorescence imaging is the capability of fluorescent probes,and small organic fluorescent probes are ideal materials for NIR-Ⅱ fluorescence imaging due to their desirable features such as rapid metabolism,low toxicity and well-defined architectures.Compared with FDA-approved NIR-I fluorophores ICG and MB,NIR-Ⅱ fluorophores CH1055,Q4 and H1 show better performance for in vivo biomedical imaging,which can guarantee their potential in clinical application.However,most NIR-Ⅱ aromatic luminophores suffer from the notorious aggregation-caused quenching(ACQ)effect in the aqueous solution due to their large donor–acceptor–donor(D–A–D)or donor–spacer–acceptor–spacer–donor(D-S-A-S-D)conjugated system,which largely hinders their biomedical applications in vivo.In this study,the first NIR-Ⅱ organic aggregation-induced emission(AIE)fluorophore HLZ-BTED,encapsulated as nanoparticles HLZ-BTED dots for in vivo biomedical imaging,was designed and synthesized.The NIR-Ⅱ AIE HLZ-BTED dots showed high temporal resolution,high photostability,outstanding water-solubility and biocompatibility in vitro and in vivo.HLZ-BTED dots were further used for the long-term breast tumor imaging,visualizing tumor-feeding blood vessels,long-term hind limb vasculature and incomplete hind limb ischemia.More importantly,as a proof-of-concept,it is the first time to perform the non-invasive and real-time NIR-Ⅱ imaging of the gastrointestinal tract in health and disease,making the AIE dots as a promising tool for gastrointestinal(GI)tract research,such as understanding healthy status of GI peristalsis,diagnosis and evaluation of intestinal motility dysfunction,assessment of drug effect on intestinal obstruction.