Optical imaging is unequivocally the most versatile and widely used visualization modality in clinical practice and research. Fluorescence imaging has received particular attention due to the increasing availability of fluorescent probes that enable the noninvasive study of gene expression, protein function, protein-protein interactions, and a large number of biological processes in real time. The importance of long wavelength and near infra-red (NIR) imaging has dramatically increased due to the desire to perform whole animal and deep tissue imaging. Fluorescence imaging relies on high performance fluorescent materials. Regarding to biocompatibility, small molecular organic fluorescent probes show much more great potential for clinical translation. However, organic fluorescent...[ Read more ]

Optical imaging is unequivocally the most versatile and widely used visualization modality in clinical practice and research. Fluorescence imaging has received particular attention due to the increasing availability of fluorescent probes that enable the noninvasive study of gene expression, protein function, protein-protein interactions, and a large number of biological processes in real time. The importance of long wavelength and near infra-red (NIR) imaging has dramatically increased due to the desire to perform whole animal and deep tissue imaging. Fluorescence imaging relies on high performance fluorescent materials. Regarding to biocompatibility, small molecular organic fluorescent probes show much more great potential for clinical translation. However, organic fluorescent materials with red or near infrared emission often suffer from aggregation-caused quenching (ACQ) effect because their elongated π-conjugation and/or strong donor-acceptor (D-A) interaction favor strong intermolecular π-π stacking that leads to emission quenching. The unique aggregation-induced emission (AIE) process not only offers a straightforward solution to the ACQ problem, but also provide a facile strategy to construct light-up/turn-on activatable probes for biomedical imaging.

There is a high demand on the developments of novel AIEgens with easy preparation and longer wavelength. In this thesis, three series of AIEgens were developed. Their working mechanism and biological imaging applications were investigated.

A new red-emissive AIEgen, abbreviated as 2TPE-4E, was designed and synthesized by jointing two diethylamine substituted tetraphenylethylene (TPE) units using polyyne (C≡C – C≡C – C≡C – C≡C) as a conjugated bridge. The working mechanism were carefully deciphered. Based on this AIEgens, two tumor-targeting nanoprobes were developed by combination with aptamer and bioorthogonal metabolic glycoengineering.

Also, a bright red-emissive AIEgen, abbreviated as TTS, was designed and synthesized. Compared to our previous developed TTD AIEgens, TTS showed much more typical AIE characteristics, which is weak or non-emissive in the solution state due to the enhanced TICT effect but several hundred-fold stronger emissive in the aggregated state. This AIEgen was further used for real-time imaging of the blood vessels of brain with deep penetration and high contrast.

Besides, inspired from the recent advance of mechanism study of tetraphenylethylene (TPE), a typical and widely-used AIEgen. We develop a new kind of D–A–D structural NIR fluorophores, TSPCI, with typical AIE behavior by bridging strong electron acceptors and strong electron donors through twisted double bond. TSPCI showed excellent NIR-II imaging performance for in vivo dynamic imaging with high contrast and penetration depth. TSPCI holds great potential as building block to easily fabricate activatable fluorescent probes with superior responsive ability in NIR-II optical window for in vivo imaging applications.