Handbook of Aggregation-Induced Emission, Volume 2. Группа авторов

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Figure 3.23 (a) Chemical structures of typical mitochondrial targeting SSB probes 39 and 40. (b) Schematic representation of intracellular tracking and the therapeutic effect of 39 in cancer cells. (c) Confocal microscopic images of HeLa cells and NIH‐3T3 cells after incubation with 39. The cells were costained with MitoTracker or LysoTracker.

      Source: Reprinted from Ref. [56] (Copyright 2014 John Wiley and Sons).

      By modifying with various targeting groups, a number of SSB‐based bioprobes for other cellular organelle‐specific imaging such as lysosome [62], cell membrane, and LDs were reported [63]. Besides, a series of SSB derivatives were also designed as photosensitizers for imaging and killing both gram‐positive and ‐negative bacteria over mammalian cells [64, 65].

Morpholine is widely used as a lysosome targeting ligand. SSB‐based bioprobes 41 and 42 thus show high affinity to lysosomes. By substituting hydroxyl groups of salicylaldehyde with acetyl groups, the ESIPT of 41 was blocked and the fluorescence was quenched. After incubating with live cells, the probes accumulated in lysosomes and subsequently the protective acetyl groups were hydrolyzed by esterase, making them a specific fluorescent probe for lysosome esterase imaging [62]. A similar lysosome‐specific SSB bioprobe 42 was developed according to the same principle and applied to monitor the autophagy process [66]. Figure 3.24B shows that the fluorescence of 42 in HeLa cells colocalized finely with commercial lysosome dye with Pearson's coefficient as 0.9. Figure 3.24C shows that even if excess 42 was removed before rapamycin treatment, the newly formed lysosomes were lit up. The results strengthen that the fusion of the autophagic region with the original lysosome occurred during autophagy, demonstrating the satisfactory application of 42 in visualization of the lysosome and lysosome‐involved autophagy process.

      LDs are subcellular organelles surrounded by a phospholipid monolayer and contain diverse neutral lipids such as triacylglycerol and cholesteryl esters. Some reports demonstrate that LD is a dynamically complex organelle involved in various physiological processes, and its metabolic balance and stability play a key role in living organisms. The abnormality of LD activities or numbers is a critical signal of various diseases, such as fatty liver diseases, type II diabetes, and inflammatory myopathy. Monitoring the location and distribution of LDs is therefore of great importance for early diagnosis of related diseases. Figure 3.24D displays two hydrophobic SSB compounds 43 and 44 applied in specific LD imaging for both live and fixed cells [67]. 43 and 44 emit yellow and orange fluorescence, respectively. Due to their ESIPT characteristics, the Stokes shift of 43 and 44 is as large as ~200 nm, which is superior to commercial BODIPY dyes for LD staining. As shown in Figure 3.24E, after incubation with 43 or 44, the LDs in A549 cells were lit up with high resolution. The overlap rates of 43 and 44 with commercial LD dyes BODIPY were as high as 0.98 and 0.97, respectively, indicating their high LD‐targeting affinity. No significant inhibition of HeLa cell growth was observed in media with high concentrations of up to 10 μM 43 and 44, indicating that these two probes have excellent biocompatibility.