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Supramolecular toroids have attracted continuous attention because of their fascinating topological structure and important role in biological systems. However, it still remains a great challenge to construct supramolecular functional toroids and clarify the formation mechanism. Herein, we develop a strategy to prepare supramolecular helical fluorescent nanotoroids by cooperative self-assembly of an amino acid and a dendritic amphiphile (AIE-den-1) with aggregation-induced emission characteristics. Mechanistic investigation on the basis of fluorescence and circular dichroism analyses suggests that the toroid formation can be driven by the interactions of AIE-den-1 with amino acid and goes through a topological morphology transformation from nanofibers to left-handed nanotoroids by means of a twist-fused-loop process.

The development of straightforward and efficient synthetic methods toward ring-fused heteroaromatic polymers with attractive functionalities has great significance in both chemistry and materials science. Herein, we develop a facile cascade C-H-activated polyannulation route that can in situ generate multiple ring-fused aza-heteroaromatic polymers from readily available monomers in an atom-economical manner. A series of complex polybenzimidazole derivatives with high absolute molecular weights of up to 24000 are efficiently produced in high yields within 2 hours. Benefiting from their unique imidazole-containing ring-fused structures with multiple aryl pendants, the obtained polymers show excellent thermal and morphological stability, good solution processability, high refractive index, small chromic dispersion, as well as remarkable acid-base-responsive fluorescence. Taking advantage of the ratiometric fluorescence response of the triphenylamine-substituted heteroaromatic polymer to pH variations, we successfully apply it as a sensitive fluorescence probe for the mapping and quantitative analysis of intracellular pH changes in live cells. Furthermore, through the simple N-methylation reaction of the ring-fused polybenzimidazoles, diverse azonia-containing polyelectrolytes are readily produced, which can efficiently kill cancer cells via the synergistic effects of dark toxicity and photo-toxicity.

The lysosomal targeted ratiometric fluorescent BD probe reveals excellent application performance in the fields of selective monitoring of the lysosome pH of living cells, real-time dynamic monitoring of autophagy, and document anti-counterfeiting.

As two important subcellular organelles in eukaryotic cells, the Golgi apparatus (GA) and endoplasmic reticulum (ER) have recently captivated much interest due to their considerable importance in many biofunctions and role as critical biomarkers for various diseases. The development of efficient GA- and ER-specific probes is of great significance, but remains an appealing yet significantly challenging task. Herein, we reported for the first time the construction of an aggregation-induced emission (AIE) platform for GA and ER fluorescent probes, termed as AIE-GA and AIE-ER, by facile synthesis and simple functionalization. Their excellent targeting specificity to GA or ER, remarkable photostability, high brightness, and low working concentration make AIE-GA and AIE-ER significantly impressive and superior to commercially available probes. Moreover, molecular docking calculations are performed to validate the targeting mechanism of the two AIE probes., As two important subcellular organelles in eukaryotic cells, the Golgi apparatus (GA) and endoplasmic reticulum (ER) have recently captivated much interest due to their considerable importance in many biofunctions and role as critical biomarkers for various diseases.

Early diagnosis of renal fibrosis is crucially significant on account of its worldwide prevalent tendency. Optical imaging in the near-infrared window has been recognized as an appealing technique for the timely detection of renal dysfunction. However, formulating a contrast agent that allows early monitoring of renal fibrosis and concurrently renally clearable in a normal group is still challenging. Herein, a nanosized fluorophore with aggregation-induced emission (AIE) features, namely AIE-4PEG550 NPs, is well-tailored and amenable to longitudinal visualization of the fibrosis progression specifically in the early-stage via short-wave infrared (SWIR, 900-1700 nm) fluorescence and photoacoustic bimodal imaging. The small size (≈26 nm), renally filtrable molecular weight (3.3 kDa), high renal clearance efficiency (93.1 ± 1.7% excretion through the kidneys within 24 h), outstanding imaging performance, and good biocompatibility, together make AIE-4PEG550 NPs remarkably impressive and far superior to clinical diagnostic assays. The finding in this study would provide a blueprint for the next generation of diagnostic agents for the extent of renal fibrosis.

A mitochondrial pH sensing fluorescent probe namely 2-(2-(6-hydroxynaphthalen-2-yl)vinyl)-3-(6-(triphenyl-phosphonio)hexyl)benzothiazol-3-ium bromide (HTBT2) was designed and facilely synthesized via the Knoevenagel condensation reaction. HTBT2 displayed a linear fluorescence enhancement at 612 nm in response to pH changes between 8.70 and 7.20. The pKa value was determined to be 8.04 ± 0.02, which might be ideal for mitochondrial pH (pHmito ∼8.0) detection. HTBT2 also exhibited a remarkable large Stokes shift of 176 nm, which could diminish the interference of excitation light. The results of live cell imaging studies suggested that HTBT2 showed excellent targeting ability for mitochondria. Importantly, it was successfully applied to visualize mitochondrial pH changes in live cells and differentiate the pHmito difference between cancer cell lines and normal cell lines. Our results consistently supported that HTBT2 held practical promise for the investigation of physiological processes related to pHmito changes and clinical potential for cancer cell differentiation.

A mitochondrial pH sensing fluorescent probe namely 2-(2-(6-hydroxynaphthalen-2-yl)vinyl)-3-(6-(triphenyl-phosphonio)hexyl)benzothiazol-3-ium bromide (HTBT2) was designed and facilely synthesized via the Knoevenagel condensation reaction. HTBT2 displayed a linear fluorescence enhancement at 612 nm in response to pH changes between 8.70 and 7.20. The pK

A lysosome-targeting and polarity-specific fluorescent probe CPM has been rationally designed for cancer diagnosis and imaging. We have successfully shown that lysosome polarity may serve as an ubiquitious marker for cancer detection. The potential of CPM for cancer diagnosis has also been demonstrated at the levels of live cells, organs, whole animal, and clinical patient tissue samples.

We present the first Golgi-targeted small-molecular pH-sensitive fluorescent probe RSG, which allows an off-on fluorescence response to Golgi acidification with high sensitivity and specificity. RSG has been successfully used for real-time monitoring of Golgi pH changes induced by drug treatment at the cellular level, as well as by the LPS-mediated inflammation in vivo.

Lysosomes are ubiquitous acidic organelles responsible for breaking down of biological substances. Acidic pH is a characteristic feature of lysosomes whereas aberrant lysosomal pH has been manifested in myriad diseases. Thus, being able to perform real-time monitoring of lysosomal pH is crucial to understand and investigate pathological and physiological processes. Herein, we report a novel and efficient carbazole-benzimidazole-based two-photon ratiometric fluorescence probe, namely BIMC for fast-response lysosomal pH detection and imaging. In this probe, the methylcarbitol substituent serves as a targeting unit for lysosomes and the benzimidazole moiety acts as a proton reaction site. BIMC exhibits an ideal pKa value of 4.46, which is found useful for quantitative detection and imaging of lysosomal pH change in the linearly proportional range of 3.8–5.0. Two-photon ratiometric imaging studies shows that BIMC can selectively monitor pH with excellent photostability and low cytotoxicity in the lysosomes of live cells and in living cancer tissues. All these results demonstrate that BIMC is a promising two-photon fluorescent probe for a practical use in investigating lysosome-associated pathological and physiological processes.

A novel quinoline/benzothiazole pH probe (E)-2-(2-(quinolin-4-yl)vinyl)benzothiazole (BTVQ) was facilely synthesized. BTVQ exhibits remarkable emission response to pH and can image pH changes within the extreme acidity range of 3.0–3.8 with a pKa of 3.52. Moreover, BTVQ displays a notably large Stokes shift of 110 nm, which can reduce the excitation interference. BTVQ was successfully applied in HeLa cells and E. coli cells, suggesting that BTVQ can be employed as one of the few lysosome specific probes for imaging acidic intracellular pH changes, especially under extreme-acidity conditions in bacteria.

A facile Schiff-base ligand 8-hydroxyjulolidine-pyridyl hydrazone ( L ) as the fluorescent probe was synthesized and characterized. L was selective toward Al3+ ions with a visible color change from pale-to-yellow and fluorescence enhancement at 480 nm. L forms complex with Al3+ in 1:1 ratio as supported by Job’s plot analysis and ESI-MS. The binding mode was further confirmed by 1H NMR titrations. The detection limit was calculated to be 8.22×10−8 M for Al3+. These merits of L , i.e., requiring facile one-step synthesis and displaying high sensitivity make L a promising candidate as a chemosensor for Al3+ion.

Lysosomes are acidic organelles containing many hydrolytic enzymes responsible for degrading macromolecules. Aberrant lysosomal pH changes are known to associate with lysosomal dysfunctions linking to various diseases including cancer and neurodegenerative disorders. Thus, it is of paramount importance to monitor lysosomal pH changes in order to investigate the pathological conditions. We report herein two novel, highly sensitive and fast responsive carbazole-based ratiometric fluorescent probes with different emission wavelengths, namely MCDBI and MCDI for lysosomal pH detection and imaging. Importantly, the MCDBI and MCDI probes bearing indole and benzoindoles as acid-sensing sites exhibit pKa values of 4.26 and 4.51, respectively, which are ideal for the quantitative analysis of lysosomal pH changes in living cells. These probes exhibited a strong pH-dependent behavior and responded linearly and rapidly to minor pH fluctuations. Moreover, the two biocompatible probes are highly lysosomal targeting, sensitive towards H+ over metal ions and some bioactive molecules, and exhibit excellent photostability and good reversibility. These probes have excellent cell membrane permeability and are further applied successfully to monitor lysosomal pH fluctuations in the lysosomes of HepG2 cells.

Mitochondrial membrane potential (MMP) is a critical parameter representing mitochondrial function and cellular activities. The development of a robust and convenient method for real-time tracking the MMP changes is still highly desirable and urgently needed. Herein, we presented a novel mitochondria-lysosomes migration fluorescent probe (CSP) with aggregation-induced emission (AIE) characteristics and near-infrared (NIR) solid-state emission for in situ real-time tracking MMP variations. The cationic probe CSP exclusively stained mitochondria with normal MMP; once MMP decreases, CSP could be released from mitochondria and migrated to lysosomes; with the recovery of MMP, CSP could move back to the mitochondria. Interestingly, the average colocalization coefficient (CLC) between CSP and a commercial lysosome-specific dye (LB-NIR) have been successfully served as a reliable and practical MMP parameter for real-time tracking the dynamic changes of MMP. Moreover, other unique features of AIEgens such as large Stokes shift (197 nm), high fluorescence quantum yield (9.8 %), excellent photostability and wash-free bioimaging, together make CSP a promising tool for real-time tracking MMP during the mitochondria-involved pathophysiologic processes.

Intracellular pH, especially cytoplasmic pH (~7.2) plays a crucial role in cell functions and metabolism. A ratiometric fluorescent probe namely, 6-(2-(benzothiazol-2-yl)vinyl)naphthalen-2-ol (BTNO) was facilely synthesized by the condensation of 6-hydroxy-2-naphthaldehyde and 2-methylbenzothiazole. BTNO exhibited a remarkable ratiometric emission (F456/F526) enhancement in response to a pH change with a linear range of pH = 9.50–7.00 and a pKa value of 7.91 ± 0.03, which is desirable for measuring and monitoring the cytoplasmic pH fluctuations. In addition, because of the high fluorescence quantum yield of BTNO (Φ = 0.88 in DMSO and 0.61 in water relative to quinine sulfate solution in 0.1 M H2SO4), the interferences of the probe on the physiological functions could be greatly reduced. This could also provide enhanced measurement sensitivity. The successful demonstration of BTNO in detecting and monitoring the intracellular pH changes in live HeLa cells via a ratiometric approach confirmed that BTNO held a practical potential in biomedical research.

A mitochondrial-targeted pH fluorescent probe 4-(2-(6-hydroxynaphthalen-2-yl)vinyl)-1-methylpyridin-1-ium was facilely synthesized via the carbon–carbon double bond bridging of 6-hydroxy-2-naphthaldehyde and 1,4-dimethylpyridinium iodide salt. The probe exhibited remarkable pH-dependent behavior in the linear range of 7.60–10.00, with a pKa value of 8.85 ± 0.04 near mitochondrial pH. A significantly large Stokes shift of 196 nm was obtained, which reduces the interference of excitation light. Application of the probe in live HepG2 cells indicated that the probe had excellent mitochondrial targeting ability and was successfully used to visualize mitochondrial pH fluctuations in live cells.

A facile, economical and green one-step hydrothermal method for N-doped CDs is presented by using citric acid as carbon source and urea as nitrogen source. The as-prepared N-doped CDs possess an average size of 5.23 nm and exhibit a high fluorescent quantum yield of 25.4%, good water solubility, and excellent photostability. The fluorescence of N-doped CDs may be quenched dramatically from curcumin via the inner filter effect. The sensitive detection method of curcumin in aqueous solution was developed with the linear range of 2.0 × 10−7 to 1.0 × 10−5 mol L−1 and detection limit of 8.48 × 10−8 mol L−1 (S/N = 3). The other common ions and related compounds could not interfere with the detection of curcumin enabling good selectivity. The proposed method was successfully applied to the determination of curcumin in urine samples and the recoveries were 95.71–103.81%.

As an effective lysosomal biomarker for oxidative stress status, cysteine (Cys) plays an important role in lysosomal proteolysis. Herein, we report the first lysosome-targetable fluorescence probe (MCAB) for Cys-selective detection based on nucleophilic addition reaction of sulfhydryl toward a α, β-unsaturated ketone and demonstrate its application to lysosomal-targetable imaging. MCAB is designed based on a α, β-unsaturated ethanoylcarbazole as the fluorophore and the thiols reaction site, and a methylcarbitol unit as a lysosome-targetable group. Upon reacting with Cys, this probe turns on highly specific fluorescence signals linearly proportional to Cys concentrations over the range of 0–300 μM. MCAB detects Cys with a rapid response time (within 12 min) and low limit of detection (0.38 μM). MCAB is highly selective to Cys over other similar biothiols including homocysteine (Hcy) and glutathione (GSH). Moreover, it also exhibits significant lysosomal-targetable ability, which is ideal for lysosomal Cys-selective imaging. Using MCAB, we have successfully visualized the fluctuation endogenous Cys in lysosomes under oxidative stress status in real-time.