Covalent organic framework-MnO2 nanoparticle composites for shape-selective sensing of bithiols.

Covalent organic frameworks (COFs) for detecting biological macromolecules in water or biological environments are generally challenging. In this work, a composite material IEP-MnO2 is obtained by combining manganese dioxide (MnO2) nanocrystals and a fluorescent COF (IEP), which is synthesized by using 2,4,6-tris(4-aminophenyl)-s-triazine and 2,5-dimethoxyterephthalaldehyde. By the addition of biothiols, such as glutathione, cysteine or homocysteine with different sizes, the fluorescence emission spectra of IEP-MnO2 changed ("turn-on" or "turn-off") via different mechanisms. The fluorescence emission of IEP-MnO2 increased in the presence of GSH by the elimination of the FRET (Förster resonance energy transfer) effect between MnO2 and IEP. Surprisingly, due to the formation of a hydrogen bond between Cys/Hcy and IEP, the fluorescence quenching for IEP-MnO2 + Cys/Hcy may be explained via the photoelectron transfer (PET) process, which endows IEP-MnO2 with specificity in distinguishing the detection of GSH and Cys/Hcy compared to other MnO2 complex materials. Therefore, IEP-MnO2 was used to detect GSH and Cys in human whole blood and serum, respectively. The limit of detection for GSH in whole blood and Cys in human serum was calculated to be 25.58 µM and 4.43 µM, which indicates that IEP-MnO2 can be used to investigate some diseases related to GSH and Cys concentration. Moreover, the research expands the application of covalent organic frameworks in the fluorescence sensing field.

A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy.

We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle-specific photosensitizers provide an excellent strategy to enhance PDT.

High-performance photocatalytic peroxymonosulfate activation by carbon quantum dots via precise surface chemistry regulation: Insight into the structure-function relations.

Carbon quantum dots (CQDs) are considered promising metal-free green catalysts for the activation of persulfates, but direct experimental evidence to identify the true active sites on the surface of CQDs is still lacking. We prepared CQDs with different oxygen contents by controlling the carbonisation temperature, using a simple pyrolysis method. Photocatalytic activity experiments show that CQDs200 exhibits the best PMS activation performance. By investigating the relationship between the oxygen functional groups on CQDs surface and photocatalytic activity, it was postulated that the C=O groups might be the predominant active site, which was confirmed by selective chemical titrations of the C=O, C-OH and COOH groups. Furthermore, limited to the weak photocatalytic properties of the pristine CQDs, ammonia and phenylhydrazine were used to precisely nitrogen-modify the o-CQD surface. We found that phenylhydrazine-modified o-CQDs-PH promoted the absorption of visible light and the separation of photocarriers, thus enhancing the activation of PMS. Theoretical calculations provide more insights from different levels of the pollutant, fine-tuned CQDs, and their interactions.

A novel dual-capability naphthalimide-based fluorescent probe for Fe3+ ion detection and lysosomal tracking in living cells.

We design and synthesize a novel 1,8-naphthalimide-based fluorescent probe MNP that features the dual capabilities of tracking lysosomes in living HeLa cells and sensitively detecting Fe3+ ions in aqueous solution. The MNP is obtained by modifying the morpholine group with a lysosomal targeting function and the piperazine group with an Fe3+ ion recognition function on the 1,8-naphthalimide matrix. In the presence of Fe3+ ions, the MNP acts as a recognition ligand to coordinate with the central Fe3+ ion, and the protonated [MNPH]+ is eventually generated, in which significant fluorescence enhancements are observed due to the intramolecular photo-induced electron transfer (PET) process being blocked. The limit of detection of Fe3+ ions is as low as 65.2 nM. A cell imaging experiment shows that the MNP has low cytotoxicity and excellent lysosomal targeting ability. Therefore, the MNP offers a promising tool for lysosomal tracking and relevant life process research.

Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe.

Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.

Near-infrared probe for early diagnosis of diabetic complications-nephropathy and in vivo visualization fluorescence imaging research.

Diabetic nephropathy is one of the common complications of diabetes, which has high risk of renal function. Dipeptidyl peptidase 4 (DPP4) is considered to be one of the good dynamic monitoring indicators for early diabetic nephropathy. Therefore, real-time monitoring of changes in the activity of DPP4 in organisms is helpful to the diagnosis and treatment of diabetes and its complications-diabetic nephropathy. A near-infrared fluorescent probe GP-DCMNH2 is designed to detect the activity of DPP4. GP-DCMNH2 is catalyzed and hydrolyzed by DPP4 into the near-infrared fluorescent dye DCMNH2, to achieve the purpose of detecting DPP4 in organisms. Based on the excellent near-infrared spectroscopy characteristics displayed by the probe GP-DCMNH2 in vitro, in living cells and diabetic mouse models, GP-DCMNH2 has been further applied in the visual fluorescence imaging of diabetic complications-diabetic nephropathy. Compared with the control group and the treatment group, GP-DCMNH2 showed a stronger near-infrared fluorescence signal in the kidney tissue and blood of diabetic nephropathy mice. Because GP-DCMNH2 shows high sensitivity in real-time dynamic monitoring of changes in the activity of DPP4 in organisms, and shows strong practicability in the spectral test of mouse models of diabetes and diabetic nephropathy. In clinical medicine, GP-DCMNH2 is expected to be used in the early diagnosis, prevention and treatment of diabetes and diabetic nephropathy.

A Novel Fluorescent Probe Strategy Activated by ß-Glucuronidase for Assisting Surgical Resection of Liver Cancer.

Liver cancer is a primary malignant tumor with a very high fatality rate, which has seriously threatened human health and life. In normal hepatocellular lesions, ß-glucuronidase (GLU) activity in liver cancer tissues is significantly increased. Therefore, GLU has become one of the important biomarkers of primary liver cancer. Here, a series of fluorescent probes (DCDH, DCDCH3, DCDOCH3, and DCDNO2) for early diagnosis of liver cancer and auxiliary surgical resection were successfully synthesized. Since the electron-withdrawing group -NO2 connected to the probe DCDNO2 accelerates the rapid cleavage of the glycosidic bond, DCDNO2 exhibits superior fluorescence properties that are more sensitive and rapid than the other three probes DCDH, DCDCH3, and DCDOCH3 when detecting GLU. DCDNO2 has been well-applied in real-time fluorescent visualization imaging for the detection of GLU activity in liver cancer cells and tumor tissues. In addition, DCDNO2 has also been successfully used in the early diagnosis of liver cancer and real-time imaging to guide the surgical resection of liver cancer tumors. Therefore, DCDNO2 has great potential for development in bioclinical medicine for the early detection and treatment of liver cancer.

Covalent Organic Frameworks Doped with Different Ratios of OMe/OH as Fluorescent and Colorimetric Sensors.

Improving the luminescence properties of covalent organic frameworks (COFs) has always been an important issue. Here, a series of COFs (([OMe]x -TzDa (TzDa is composed only by monomerics Tz and Da, OMe represents the incorporation of monomeric Dm)) with different ratios of OMe and OH were designed and synthesized. The photochemical behavior of [OMe]x -TzDa changed significantly due to the synergistic effect of aggregation induced emission (AIE), intramolecular charge transfer (ICT), and excited-state intramolecular proton transfer (ESIPT) effects. [OMe]2 -TzDa, which contained a ratio of 2/1 of OMe/OH, showed the strongest fluorescence emission in water and the best linear relationship for the detection of pH. Furthermore, [OMe]2 -TzDa was used to monitor HCl and NH3 gases and showed a color change, visible to the naked eye. Therefore, a "confidential pigment" was successfully made. Moreover, [OMe]2 -TzDa was also applied to detect N2 H4 . The work indicates the [OMe]2 -TzDa can serve as the first fluorescence sensor to detect pH, HCl and NH3 gases, which also shows a good response to N2 H4 .

Structural Engineering of Covalent Organic Frameworks Comprising Two Electron Acceptors Improves Photocatalytic Performance.

Covalent organic frameworks (COFs) have recently attracted much attention as potential photocatalysts for hydrogen production. The effective separation of photogenerated charges is a key objective to improve the photocatalytic activity of COFs. Here, four COFs were synthesized through the Schiff-base reaction to investigate whether the presence (simultaneous or not) of triazine and ketone as acceptors in COFs improved electron-hole separation efficiency. Evidence indicated that charge separation was more efficient when triazine and ketone were simultaneously present in the COF. The COF comprising two acceptors displayed the highest photocatalytic hydrogen production rate (31.43 µmol h-1 ; 41.2 and 3.4 times as large as those of the COFs containing only triazine or ketone, respectively). Moreover, the effect of the distance between the two acceptors on the electron-hole separation was investigated by changing the length of a bridging biphenyl ring. It turned out that the transport distance of a single phenyl group was more favorable for the catalytic reaction. This work affords insight and support for the design of efficient COF photocatalysts.

Long-Wavelength Ratiometric Fluorescent Probe for the Early Diagnosis of Diabetes.

Diabetes is a metabolic disease caused by high blood sugar. Patients are often suffering from high blood pressure and arteriosclerosis, which may even evolve into liver disease, kidney disease, and other diabetic complications. Dipeptide peptidase IV (DPP-IV) plays an important role in regulating blood sugar levels and is one of the targets for the diagnosis and treatment of diabetes. Here, a long-wavelength ratiometric fluorescent probe DCDHFNH2-dpp4 for detecting DPP-IV was designed and synthesized. DCDHFNH2-dpp4 was used to detect DPP-IV in healthy, tumor-bearing, and diabetic mice, and only diabetic mice showed strong fluorescence signals. In organ imaging, it is found that DPP-IV is relatively enriched in the liver of diabetic mice. In addition, probe DCDHFNH2-dpp4 also exhibited a significant ratiometric fluorescence signal in the serum of diabetic mice. Therefore, the fluorescent probe DCDHFNH2-dpp4 has shown outstanding potential in the early diagnosis of diabetes, and DCDHFNH2-dpp4 is hopeful to be applied to actual clinical medicine.

In vivo imaging via a red-emitting fluorescent probe to diagnosing liver cancer or drug-induced liver disease.

Leucine aminopeptidase (LAP) as an important proteolytic enzyme, has been mainly found in hepatobiliary cells, and overexpressed in hepatoma cells. Herein, a new highly selective red-emitting fluorescent probe (DCDHF-Ala) for LAP has been synthesized based on 2-dicyanomethyldiene-3-cyano-2, 5-dihydrofuran (DCDHF) as fluorophore, and alanine (Ala) as the detection group. More importantly, it's the first time to use Ala as a reactive group for LAP. DCDHF-Ala has a low detection limit (0.20 U/L), excellent water solubility and cell membrane permeability. In addition, the probe has been successfully applied to fluorescent imaging in cells and zebrafish. It's especially worth mentioning that, DCDHF-Ala has a high biosafety and enables a real-time detection of LAP levels in mice model. What's the most important is that DCDHF-Ala may be an effective tool to qualitatively monitor the upregulation of LAP induced by liver injury and liver cancer.

A ratiometric fluorescent sensor for rapid detection of the pyroglutamate aminopeptidase-1 in mouse tumors.

Pyroglutamate aminopeptidase-1 (PGP-1) is an important enzyme that plays an indispensable role in the process of inflammation. Up to now, few reports have been reported on the detection of PGP-1 activity in vivo and in vitro, and there are no reports on ratiometric detection. Here, the first red-emitting ratiometric fluorescent sensor (DP-1) for the specific detection of PGP-1 both in vivo and in vitro was designed and synthesized by using DCD-NH2 as the luminescent parent and pyroglutamate as a recognition group. After interacting with PGP-1, the amide bond is hydrolyzed by the enzyme and the color of the solution changes from yellow (λabs = 420 nm) to red (λabs = 520 nm), accompanied by obvious fluorescence emission wavelength change (from ∼564 nm to ∼616 nm). The probe has high specificity and sensitivity towards PGP-1 in about 10 min, and the DL is as low as 0.25 ng mL-1. Interestingly, under the stimulation of Freund's incomplete adjuvant and lipopolysaccharide, the imaging of DP-1 in HepG2 and RAW264 cells shows that the expression of PGP-1 is associated with inflammation. What's more, for the first, the imaging of a mouse tumor model confirms that the enzyme is closely related to the occurrence of some inflammation and tumor diseases. These results indicate that DP-1 can be used as an effective tool for real-time monitoring of PGP-1 levels both in vivo and in vitro and the study of inflammatory tumor pathology.

Nanoscale Metal-Organic Layers Detect Mitochondrial Dysregulation and Chemoresistance via Ratiometric Sensing of Glutathione and pH.

Mitochondrial dysregulation controls cell death and survival by changing endogenous molecule concentrations and ion flows across the membrane. Here, we report the design of a triply emissive nanoscale metal-organic layer (nMOL), NA@Zr-BTB/F/R, for sensing mitochondrial dysregulation. Zr-BTB nMOL containing Zr6 secondary building units (SBUs) and 2,4,6-tris(4-carboxyphenyl)aniline (BTB-NH2) ligands was postsynthetically functionalized to afford NA@Zr-BTB/F/R by exchanging formate capping groups on the SBUs with glutathione(GSH)-selective (2E)-1-(2'-naphthyl)-3-(4-carboxyphenyl)-2-propen-1-one (NA) and covalent conjugation of pH-sensitive fluorescein (F) and GSH/pH-independent rhodamine-B (R) to the BTB-NH2 ligands. Cell imaging demonstrated NA@Zr-BTB/F/R as a ratiometric sensor for mitochondrial dysregulation and chemotherapy resistance via GSH and pH sensing.

Red emission ratio fluorescent probe for the activity of vanin-1 and imaging in vivo.

Pantetheinase, also known as Vanin-1, catalyzes pantetheine to decompose into the precursor of CoA - pantothenic acid and aminothiol cysteamine. Studies have shown that Vanin-1 plays an important role in many important physiological pathologies. In this paper, a new red emission ratio fluorescent probe DCM-PA (I640 nm/I564 nm) has been implemented to detect the activity of Vanin-1 in cells and vivo. DCM-PA has short response time (30 min), high selectivity and low sensitivity (DL =0.69 ng/mL). Also, we have applied DCM-PA for imaging in cells and mice, and the results have indicated that the probe has a non-negligible potential for monitoring the activity of Vanin-1 in situ, benefiting further to study the role of Vanin-1 in physiology and pathology. In addition, the up-regulation of this enzyme by starvation confirmed the inevitable connection between diabetes and abnormal expression of Vanin-1.

Multifunctional Near-Infrared Fluorescent Probes with Different Ring-Structure Trigger Groups for Cell Health Monitoring and In Vivo Esterase Activity Detection.

A series of multifunctional ratiometric near-infrared fluorescent probes (CYOH-3, CYOH-4, CYOH-5, and CYOH-6) for esterase detection are designed by gradually changing the deflection of the plane twist in the molecule. These probes are composed of different ring-structure trigger groups (from three-membered ring to six-membered ring) and the same luminescent group CYOH. These probes show maximum absorption at ∼585 nm and a fluorescence emission peak at ∼655 ± 5 nm. In the presence of esterase, the probes were hydrolyzed to expose the fluorophore CYOH (λabs = 690 nm, λem = 710 ± 5 nm), thus exhibiting ratiometric near-infrared fluorescence. The probe CYOH-6 has lower plane deflection angle and better ratiometric (R = I710±5nm/I657±4nm) fluorescence properties than probes CYOH-3, CYOH-4, and CYOH-5. CYOH-6 (six-membered ring) has been successfully used to target esterase in mitochondria and distinguish between dead cells (esterase inactivation) and live cells. In addition, CYOH-6 has been well used for monitoring of esterase activity in zebrafish and mice, which proves that these probes have good prospects for clinical biomedical applications.

Activity-based ratiometric fluorescent small-molecule probe for endogenously monitoring neutrophil elastase in living cells.

Neutrophil elastase (NE), a representative protease which is closely related to many diseases, acts an indispensable role in inflammatory diseases and clinical medicine. In this work, one activity-based non-peptide ratiometric fluorescent probe DCDF was designed with pentafluoropropionic anhydride as identification group. To our knowledge, this is the first probe capable of detecting NE in ratio. After the addition of the NE, the emission spectrum of DCDF has obvious bathochromic-shift phenomenon, and there is large Stokes shifts of ∼60 nm. Compared to only a few reported NE probes, DCDF is sensitive and selective and has very low detection limit (0-14 µg/mL, DL = 30.8 ng/mL). A possible response mechanism was proposed and verified by HPLC and HRMS spectra. What's more, DCDF is capable of endogenous recognition imaging in biological cells without interference from other enzymes under the ratio signal. A549 and HeLa cells were used for endogenous cell imaging experiments of NE and the feasibility of DCDF for the specific detection of NE in cells was proved. This experimental result makes probe DCDF a very promising tool for the clinical diagnosis and treatment of NE related diseases.

Visible to Near-Infrared Emission Ratiometric Fluorescent Probe for the Detection of Vanin-1 In Vivo.

Pantetheinase (Vanin-1) is an ectoenzyme, which involves the metabolic pathway of coenzyme A (CoA), and can decompose pantetheine into pantothenic acid (CoA precursor) and aminothiol cysteamine. Previous studies have revealed that Vanin-1 with essential biological functions is closely related to many diseases. However, the lack of simple and effective detection methods has severely hindered the further study of Vanin-1's physiological functions. In this work, we have developed a near-infrared (NIR) emission ratio fluorescent probe TMN-PA (I645 nm/I568 nm) that enables us to detect Vanin-1 rapidly (in 15 min) with a minimum detection limit of 0.37 ng/mL. What is more, this probe shows excellent potential in in situ real-time monitoring of the endogenous Vanin-1, contributing to further research on Vanin-1 and understanding its mechanisms in physiological pathology. To our knowledge, this probe is the first NIR emission ratio (I645 nm/I568 nm) fluorescent probe ever reported to monitor the activity of Vanin-1 in vivo.

BODIPY-based asymmetric monosubstituted (turn-on) and symmetric disubstituted (ratiometric) fluorescent probes for selective detection of phosgene in solution and gas phase.

Here, we designed and synthesized two fluorescent probes for detecting phosgene by nucleophilic substitution reaction using BODIPY as a fluorophore and 2-aminobenzylamine as reactive functional group. For the first time, we have studied the similarities and differences between asymmetric monosubstituted (1) and symmetric disubstituted (2) probes. A monosubstituted probe 1 (having a 2-aminobenzylamine group at the 3-position of BODIPY) has fluorescence-enhancing (weak green fluorescence to strong green fluorescence) responce to phosgene in 30 s with a large Stokes shift (∼70 nm) and sensitive property (DL = 0.81 nM); while the disubstituted probe 2 (having two 2-aminobenzylamine groups at the 3, 5-position of BODIPY) has a ratiometric fluorescent responce to phosgene in 2 min. The linear range of the response is wider than that of the monosubstitution probe 1, and the detection limit is also lower (2.36 nM). In addition, probes 1 and 2 can effectively eliminate the interference of other substances with similar chemical structure as phosgene. They can not only detect phosgene in solution environment, but also in gaseous environment quickly and sensitively.

Porous Organic Polymers Containing a Sulfur Skeleton for Visible Light Degradation of Organic Dyes.

Three novel chemically stable porous organic polymers (POPs) were synthesized by the hydrothermal method; the POPs contain sulfone bonds (TpSD), no sulfur atoms (TpMD), or thioether bonds (TpTD). The catalytic mechanism of the POP with sulfone bonds was studied, and it was found that the wide visible light absorption range, high specific surface area, and the hydrophilicity of the material significantly promoted the catalytic efficiency of TpSD. The presence of O=S=O gives TpSD a higher degree of conjugation than TpMD and TpTD, so TpSD shows the strongest UV/Visible absorption and faster transmission of electrons. The photocatalytic degradation of Rhodamine B (RhB) molecules is approximately 100 % with TpSD and its pseudo-first-order rate constant is 0.0770 min-1 , which is the highest among all reported non-metallic photocatalysts. Moreover, it is also the first time that sulfur-containing polymer have been used in photocatalytic degradation of dyes.

Dually emitting carbon dots as fluorescent probes for ratiometric fluorescent sensing of pH values, mercury(II), chloride and Cr(VI) via different mechanisms.

The authors describe the preparation of carbon dots (CDs) that display both blue (~ 410 nm) and yellow (~ 565 nm) emission peaks. The CDs was synthesized by solvothermal treatment of o-phenylenediamine in aqueous ethyl alcohol at pH ~7.0. The CDs are shown to be useful fluorescent probes for pH values in that the ratio of fluorescences at 565 and 410 nm strongly depends on the pH value in the range from 4.5-6.5 and 10.0-13.0, respectively. The blue fluorescence is quenched by 91% by 100 µM solutions of Hg(II) through an electron transfer process, and is restored by 97% an addition of chloride (0.5 mM). The yellow fluorescence, in contrast, is hardly affected. The ratio of fluorescences at 414 and 565 nm drops linearly in the 30 to 60 µM of Hg(II) concentration range, and the limit of detection is 60 nM. Fluorescence is linearly restored in the 70 to 180 µM chloride concentration range, and the LOD is 2.8 nM. Both the blue and the yellow emission are reduced by Cr(VI) (chromate) due to an inner filter effect at pH 3.0. The ratio of fluorescences (410/565 nm) drops linearly in the 20 to 250 µM Cr(VI) concentration range, and the LOD is 260 nM. The method was utilized to analysis of chloride in salt lake brine and of Cr(VI) in spiked tap water. Graphical abstract Schematic presentation of carbon dots with pH-dependent dual emission (at ~ 410 nm and ~ 565 nm). They are shown to be viable fluorescent probes for ratiometric sensing of pH values, mercury(II), chloride and Cr(VI) via different mechanisms.