Photostable pH-Sensitive Near-Infrared Aggregation-Induced Emission Luminogen for Long-Term Mitochondrial Tracking

Abstract

Mitochondria are crucial in the process of oxidative metabolism and apoptosis. Their morphology is greatly associated with the development of certain diseases. For specific and long-term imaging of mitochondrial morphology, we synthesized a new mitochondria-targeted near-infrared (NIR) fluorescent probe (TPE–Xan–In) by incorporating TPE with a NIR merocyanine skeleton (Xan–In). TPE–Xan–In displayed both absorption (660 nm) and emission peaks (743 nm) in the NIR region. Moreover, it showed aggregation-induced emission properties at neutral pH and specifically illuminated mitochondria with good biocompatibility, superior photostability, and high tolerance to mitochondrial membrane potential changes. With a pH-responsive unit, hydroxyl xanthene (Xan), the probe exhibited a pH-sensitive fluorescence emission in the range of pH 4.0–7.0, which indicated its potential in long-term tracking of pH and morphology changes of mitochondria in the biomedical research studies.

Stimuli‐Responsive AIEgens

“…[ 220 ] Since the functions of mitochondria are highly dependent on the intracellular pH, it is greatly desirable to discriminate mitochondria at different pH values to investigate the relationship between morphology of mitochondria and intercellular pH changes. [ 219 ] Recently, Meng et al. incorporated AIE‐active TPE with a NIR merocyanine skeleton and designed a new pH‐sensitive AIEgen (TPE−Xan−In) for specific and long‐term imaging of mitochondrial morphology ( Figure a).…”

“…incorporated AIE‐active TPE with a NIR merocyanine skeleton and designed a new pH‐sensitive AIEgen (TPE−Xan−In) for specific and long‐term imaging of mitochondrial morphology ( Figure a). [ 219 ] The mechanism for its pH‐responsive behavior is that the protonation/deprotonation of the phenolic hydroxyl group in hydroxyl xanthene could switch the occurrence of intramolecular charge transfer and result in a pH‐sensitive emission from pH 4.0 to 7.0. As shown in Figure 24b, the emission peak of TPE−Xan−In in the aggregate state gradually shifted from 730 to 750 nm with the increase of pH.…”

A Type of Atypical AIEgen Used for One-Photon/Two-Photon Targeted Imaging in Live Cells

“…Since then, several propeller-like AIE luminogens (AIEgens) have successively been developed, including tetraphenylethene (TPE), tetraphenylpyrazine (TPP), hexaphenylsilole (HPS), 1,1-dimethyl-2,3,4,5-tetraphenylsilole (DMTPS), tetraaryl-1,4-dihydropyrrolo­[3,2- b ]­pyrrole (AAPP), and tetraphenyl-1,4-butadiene (TPBD) (Scheme ). − Notably, all the basic AIEgens shown in Scheme are composed of symmetric propeller-like structures centered on small conjugated or small heteroaromatic cores. Up to now, AIEgens with a large electron D–A conjugated system have almost all been derived from the basic and structurally limited AIE cores such as tetraphenylethene (TPE) and tetraphenylpyrazine (TPP).…”

Enhancement of the Aggregation-Induced Emission by Hydrogen Bond for Visualizing Hypochlorous Acid in an Inflammation Model and a Hepatocellular Carcinoma Model

“…The reported fluorescent probes can be used for sensing HClO on the basis of many chromophores, such as BODIPY (boron-dipyrromethene), rhodamine, and cyanine. − Generally, the limitations of fluorescence molecular probes for imaging in vivo include the short emission wavelength, fair photostability, and the interference of background fluorescence. AIEgens (aggregation-induced emission luminogens) can solve these problems on the basis of a different luminous mechanism. − The aggregation emission of AIEgens can be tuned to the near-infrared range by linkage of electron donors and acceptors. − Because of the aggregation status of AIEgens, they show good photostability. , Dispersive AIEgens show weak fluorescence, but they show strong fluorescence after they penetrate and aggregate in the cells and organs. This kind of fluorescence can increase the contrast inside and outside the cells, and the background interference can be decreased …”

“…29−31 Because of the aggregation status of AIEgens, they show good photostability. 32,33 Dispersive AIEgens show weak fluorescence, but they show strong fluorescence after they penetrate and aggregate in the cells and organs. This kind of fluorescence can increase the contrast inside and outside the cells, and the background interference can be decreased.…”