Facile Synthesis of Red/NIR AIE Luminogens with Simple Structures, Bright Emissions, and High Photostabilities, and Their Applications for Specific Imaging of Lipid Droplets and Image‐Guided Photodynamic Therapy

Abstract

Red/near-infrared (NIR) fluorescent molecules with aggregation-induced emission (AIE) characteristics are of great interest in bioimaging and therapeutic applications. However, their complicated synthetic approaches remain the major barrier to implementing these applications. Herein, a one-pot synthetic strategy to prepare a series of red/NIR-emissive AIE luminogens (AIEgens) by fine-tuning their molecular structures and substituents is reported. The obtained AIEgens possess simple structures, good solubilities, large Stokes shifts, and bright emissions, which enable their applications toward in vitro and in vivo imaging without any pre-encapsulation or -modification steps. Excellent targeting specificities to lipid droplets (LDs), remarkable photostabilities, high brightness, and low working concentrations in cell imaging application make them remarkably impressive and superior to commercially available LD-specific dyes. Interestingly, these AIEgens can efficiently generate reactive oxygen species upon visible light irradiation, endowing their effective application for photodynamic ablation of cancer cells. This study, thus, not only demonstrates a facile synthesis of red/NIR AIEgens for dual applications in simultaneous imaging and therapy, but also offers an ideal architecture for the construction of AIEgens with long emission wavelengths.

A Strategy of “Self‐Isolated Enhanced Emission” to Achieve Highly Emissive Dual‐State Emission for Organic Luminescent Materials

“…[9][10][11] However, it should be mentioned that, although most traditional OLMs with ap lanar andp olycyclic conjugated framework, such as 4,5-dibromofluorescein (DBF), can exhibit highly emissive features in the well-dissolved solution state, weako rt otally quenched emission usually occurs in aggregated solid states for the aggregation-causedq uenching (ACQ) effectd ue to the existence of strong intermolecular p-p stacking (Figure 1), [12] thus making it at ough goal to achievet he highly emissive dual-state emission (both the solution state and aggregated state) for OLMs. [13][14][15] According to the AIE nature in aggregated states, [16][17][18][19][20] AIEgens with intramolecular charge-transfer (ICT) features could also be emissive in the solution state [21,22] and are thought to achievet he dual-state emissiona nd thus open an ew chapter in the exploration of OLMs in future applications.R ecently,o ur group also demonstratedt hat employing flexible alkyl chains in the conjugated molecules, such as ACQ fluorophores,c an effectively isolate their closely packed molecular backbones and thereby suppress the p-p stacking, finally leading to highly emissive lumi- Figure 1. [13][14][15] According to the AIE nature in aggregated states, [16][17][18][19][20] AIEgens with intramolecular charge-transfer (ICT) features could also be emissive in the solution state [21,22] and are thought to achievet he dual-state emissiona nd thus open an ew chapter in the exploration of OLMs in future applications.R ecently,o ur group also demonstratedt hat employing flexible alkyl chains in the conjugated molecules, such as ACQ fluorophores,c an effectively isolate their closely packed molecular backbones and thereby suppress the p-p stacking, finally leading to highly emissive lumi- Figure 1.…”

“…To overcome the notoriousA CQ effect in OLMs, Tang et al proposedt he concept of "aggregation-induced emission'' (AIE) in 2001 and then developed tremendous AIE luminogens (AIEgens), which are usually non-or weakly emissive in dilute solution, buta re intensely emissive in the aggregated states ( Figure 1). [13][14][15] According to the AIE nature in aggregated states, [16][17][18][19][20] AIEgens with intramolecular charge-transfer (ICT) features could also be emissive in the solution state [21,22] and are thought to achievet he dual-state emissiona nd thus open an ew chapter in the exploration of OLMs in future applications.R ecently,o ur group also demonstratedt hat employing flexible alkyl chains in the conjugated molecules, such as ACQ fluorophores,c an effectively isolate their closely packed molecular backbones and thereby suppress the p-p stacking, finally leading to highly emissive lumi- Figure 1. Schematic diagrams of chemical structuresf or typical OLMs (ACQ, AIE, and SIEE) and their corresponding emission photographs in THF solution or aggregated states (with aw ater fraction of 0, 50, and 99 %, respectively) and in solid state.…”

Highly Efficient Photosensitizers with Far‐Red/Near‐Infrared Aggregation‐Induced Emission for In Vitro and In Vivo Cancer Theranostics

“…Although the exploration of AIEgens in FLI‐guided PDT for cancer theranostics has achieved initial success in past few years, some major problems have yet to be solved . For instance, the majority of these AIEgens has short wavelengths of absorption and emission, therefore, aiming to the practical application of in vivo cancer theranostics, synthesis of AIEgens with intense emission in far‐red/near‐infrared (FR/NIR) region (>650 nm) exhibiting deep penetration, minimal photodamage, and high signal‐to‐noise (S/N) ratio of imaging is still required .…”

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

“…Lipid droplets are important biomarkers for many metabolic diseases, including obesity, fatty liver disease, and cardiovascular diseases . Imaging of lipid droplets by fluorescent dyes has been developed to assist diagnosis . Wang et al synthesized 1 (Figure ) to detect lipid droplets.…”

“…56 Imaging of lipid droplets by fluorescent dyes has been developed to assist diagnosis. 57 Wang et al 58 synthesized 1 (Figure 2) to detect lipid droplets. 1 is an excellent lipid droplet-specific bioprobe, and its action is attributed to the accumulation of 1 in the hydrophobic core of lipid droplets.…”