Near-infrared Fluorescent Turn-on Research Articles

Monitoring the Dynamics Fluctuations of Cysteine (Cys) Activity in Living Cells Using a Near-Infrared Fluorescence Turn-On Probe

Monitoring the Dynamics Fluctuations of Cysteine (Cys) Activity in Living Cells Using a Near-Infrared Fluorescence Turn-On Probe

A turn-on NIR fluorescence sensor for gossypol based on Yb-based metal-organic framework

The development of analytical method for selective and sensitive detection of gossypol (Gsp), an extraction from the cotton plants, is important but still challenging in food safety and medical field. Herein, we reported a turn-on near infrared (NIR) fluorescence detection strategy for Gsp based on a metal-organic framework (MOF), QBA-Yb, which was prepared from 4,4’-(quinolone-5, 8-diyl) benzoate with Yb(NO3)3·5H2O by solvothermal synthesis. The Gsp acted as another “antenna” to sensitize the luminescence of Yb3+, leading to the turn-on NIR emission upon 467 nm excitation. As Gsp concentration increased, the NIR emission at 973 nm enhanced gradually, thus enabling highly sensitive Gsp detection in a turn-on way. The experiment and theoretical calculation results revealed the presence of strong hydrogen bonds between Gsp molecules and the MOF skeleton. The developed QBA-Yb probe showed excellent characteristics for detection of Gsp molecules, accompanied by wide linear range (5–160 μg/mL), low detection limit (0.65 μg/mL) and short response time (within 10 min). We have further demonstrated that the QBA-Yb probe was successfully applied for the determination of Gsp in real samples of cottonseeds.

Dual-locking nanoprobe based on hemicyanine for orthogonal stimuli-triggered precise cancer imaging and therapy

Currently, stimulus-responsive nanomedicines are usually activated by a single cancer-associated biomarker and utilize different image/therapeutic agents for cancer imaging/therapy, which restricts the specificity of nanomedicine and complicates their design. Herein, we report a novel dual-locking theranostic nanoprobe (DL-P) based on near-infrared (NIR) hemicyanine CyNH2 with two orthogonal stimuli of cancer cell lysosomal pH (first “lock”)- and lysosome-overexpressed cathepsin B (CTB, second “lock”)-triggered NIR fluorescence turn-on and drug activation to improve the specificity of cancer imaging and therapy. The fluorescence of CyNH2 was initially quenched due to intramolecular charge transfer (ICT) but could be selectively activated under the dual-key stimulation of lysosomal pH and CTB to liberate CyNH2, resulting in strong NIR fluorescence turn-on for cancer imaging. Moreover, CyNH2 caused mitochondrial dysfunction to inhibit cancer cell proliferation in the absence of laser irradiation, which can be used in cancer therapy. Compared with previously reported probes that respond to a single stimulus, this dual-locking nanoprobe that is responsive to two orthogonal stimuli triggers with integrated imaging and therapy function in a single agent exhibits increased selectivity and specificity, which provides a prospective strategy for precise cancer imaging and therapy.

High-performance near-infrared fluorescence probe for fast and specific visualization of harmful sulfite in food, living cells, and zebrafish

Excessive sulfite is harmful to human health. To monitor the sulfite level in food, living cells, and organisms, we herein present a high-performance near-infrared (NIR) fluorescent probe DCQN that exhibits chromogenic and NIR fluorescence turn-on response towards sulfite with a rapid response time of 4.5 s, unique specificity, a low detection limit of 24 nM, and a large Stokes shift. DCQN was used for the facile and accurate determination of the sulfite level in real food with high sensitivity and good recoveries (93–105%). In particular, the sulfite present in food samples can be in situ visually detected by DCQN in terms of chromogenic reaction along with fluorescence turn-on indicator. Moreover, DCQN was incorporated into agar hydrogel to serve as a convenient, cheap and portable device for the fast and visual on-site detection of sulfite in food. Furthermore, DCQN was used to achieve in situ tracking and imaging of sulfite in MCF-7 cells and zebrafish with a high contrast ratio and high sensitivity.

Biotin-Yellow a biotin guided NIR turn-on fluorescent probe for cancer targeted diagnosis

Abstract A dicyanomethylene-4H-pyran based tumor-targeting and biothiol activatable fluorescent and colorimetric probe, named Biotin-Yellow, has been developed with unprecedented turn-on near-infrared fluorescence properties. Biotin-Yellow is non-toxic and can effectively recognize and discriminate human lung adenocarcinoma cells and urothelial (bladder) carcinoma cells from embryonic kidney cells and embryonic fibroblasts. Biotin-Yellow can also be employed for real-time bioimaging tracking of upregulated biothiol activity in cancer cells. The efficacy and biothiol responsiveness of Biotin-Yellow was further validated in vivo in zebrafish and mice xenografts.

A selective and sensitive near-infrared fluorescent probe for real-time detection of Cu(i).

The disruption of copper homeostasis (Cu+/Cu2+) may cause neurodegenerative disorders. Thus, the need for understanding the role of Cu+ in physiological and pathological processes prompted the development of improved methods of Cu+ analysis. Herein, a new near-infrared (NIR) fluorescent turn-on probe (NPCu) for the detection of Cu+ was developed based on a Cu+-mediated benzylic ether bond cleavage mechanism. The probe showed high selectivity and sensitivity toward Cu+, and was successfully applied for bioimaging of Cu+ in living cells.

A near-infrared fluorescence turn-on probe based on Michael addition-intramolecular cyclization for specific detection of cysteine and its applications in environmental water and milk samples and living cells.

Owing to its important biological functions in many physiological and pathological processes, it is necessary to develop efficient and appropriate detection methods for monitoring the levels of Cys in biological systems. Based on this, a novel rhodol-isophorone derivative (RHI) was designed and synthesized as a reaction-based fluorescence probe for specific detection of Cys with high sensitivity and large Stokes shift (155 nm). This probe was composed of an acrylate moiety (recognition group) and a rhodol-isophorone derivative (fluorophore). Probe RHI could react with Cys rapidly (15 min) with a 100-fold fluorescence enhancement. The limit of detection value was calculated to be 0.168 μM. When Cys was added, the color of the probe RHI solution turned from yellow to blue, indicating that Cys could be monitored by the naked eye. In addition, probe RHI was successfully utilized for detecting Cys in environmental water and milk samples. More importantly, the probe could be applied to imaging Cys in living cells with low cytotoxicity and good biocompatibility.

Selective detection of peroxynitrite in living cells by a near-infrared diphenyl phosphinate-based dicyanoisophorone probe.

A new NIR fluorescent probe for detection of ONOO- has been developed, which possesses a large Stokes shift, good selectivity and low cytotoxicity. This NR-ONOO probe exhibits a strong turn-on near-infrared fluorescence response toward ONOO- ion under excitation at 560nm and has been successfully applied in detecting ONOO- in living HeLa cells.

A dual-modal probe for NIR fluorogenic and ratiometric photoacoustic imaging of Cys/Hcy in vivo

Biothiols, such as cysteine (Cys) and homocysteine (Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression. In this work, we developed a near-infrared (NIR) fluorescence and photoacoustic dual-modal molecular probe ( NIR-S ) that can be specifically activated by Cys or Hcy. The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction, resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys. Thus, NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution, but also can be applied to living cells and mice to detect Hcy/Cys. This work provided a practical tool to detect Hcy/Cys levels in vivo , which would be beneficial for the early diagnosis and progress of diseases.

A near-infrared fluorescent probe based on boric acid hydrolysis for hydrogen peroxide detection and imaging in HeLa cells.

Using the characteristics of hydrogen peroxide that are able to cleave phenyl-boric acid selectively and efficiently, we here report a dicyanoisophorone-boric acid (DCP-BA)-based near-infrared (NIR) fluorescent probe for detection of hydrogen peroxide. This probe shows a rapid, highly selective, and sensitive detection process for hydrogen peroxide with a significant NIR fluorescent turn-on response that has been successfully applied to detect exogenous hydrogen peroxide in HeLa cells.

An isophorone-fused near-infrared fluorescent probe with a large Stokes shift for imaging endogenous nitroxyl in living cells and zebrafish.

Nitroxyl (HNO) plays an important role in multiple physiological and pathological processes, but the detailed generation mechanism of the endogenous HNO still remained to explore and perfect further. There is an urgent need to develop an excellent fluorescent probe for selective recognition and sensitive detection of HNO in biological systems. Near-infrared (NIR) fluorescent probes with a large Stokes shift are an ideal tool for bioimaging applications. Here, we have developed a NIR fluorescent probe with a large Stokes shift, namely, NIR-HNO, to monitor HNO in cells and zebrafish. NIR-HNO consists of an isophorone-fused NIR fluorescence reporter and a diphenylphosphinobenzoyl HNO-responsive unit. Based on an aza-ylide intramolecular ester aminolysis reaction, NIR-HNO showed a rapid selective NIR fluorescent turn-on response for HNO, high sensitivity (detection limit was 39.6 nM), and large Stokes shift (265 nm). The biological imaging results indicate that NIR-HNO is a good candidate for imaging of endogenous HNO in living systems.

Near-infrared fluorescent probe with rapid response and large Stokes shift for imaging peroxynitrite in living cells, zebrafish and mice

Detection and imaging of peroxynitrite (ONOO−) in living systems has attracted considerable attention in recent years due to its biological significance. In this paper, a new highly selective and sensitive near-infrared (NIR) fluorescent turn-on probe for ONOO− was developed. This probe uses a dicyanoisophorone-based fluorescent dye as the fluorophore and α-ketoamide as the reaction site. In the presence of ONOO−, the probe exhibits notable fluorescence enhancement at 660 nm with rapid response (<2 s), large Stokes shift (200 nm), and a low detection limit (81 nM). In addition, MTT assays indicated that this probe is of low cytotoxicity in cells, and bioimaging experiments demonstrated that the probe could be applied for imaging of ONOO− in living cells, zebrafish and mice with good imaging performance.

A highly selective and ultrafast near-infrared fluorescent turn-on and colorimetric probe for hypochlorite in living cells

Hypochlorous acid (HOCl)/hypochlorite (OCl−), important reactive oxygen species, play essential roles in many physiological and pathological progresses. Accordingly, we developed a novel dicyanomethylene-4H-pyran (DCM)-based probe DCM-OCl for colorimetric and near-infrared fluorescent turn-on detection of OCl−. The probe exhibited excellent selectivity and sensitivity for OCl− over other bio-related analytes with a detection limit of 80 nM. The excellent selectivity of DCM-OCl for OCl− was ascribed to specific oxidative cleavage of the dimethylthiocarbamate (DMTC) recognition unit by OCl−. Moreover, DCM-OCl exhibited an ultrafast turn-on response (<3 s) to OCl−, potentially allowing real-time detection of OCl−. Furthermore, DCM-OCl was successfully used to image endogenous/exogenous OCl− in living cells.

Near-infrared fluorescent probe with a super large Stokes shift for tracking CO in living systems based on a novel coumarin-dicyanoisophorone hybrid

A new near-infrared (NIR) fluorescent turn-on probe (CDCI-CO) based on a novel coumarin-dicyanoisophorone hybrid fluorophore for detection of CO both in vitro and in vivo was reported. By applying Tsuji-Trost reaction to remove the allylcarbonate group, this probe exhibits excellent capability of detecting CO in aqueous solution with rapid response, high selectivity and sensitivity, distinct NIR fluorescent turn-on signal changes at 710 nm, and a remarkable large Stokes shift of 222 nm. The detection limit of this probe for CO was determined to be as low as 33 nM. Moreover, bioimaging of CO in living cells and zebrafish with this probe was also successfully applied, indicating this probe can be used as a promising new tool for studying CO in living systems.

A near-infrared fluorescent probe for imaging endogenous carbon monoxide in living systems with a large Stokes shift

Near-infrared (NIR) fluorescent probes with a large Stokes shift are very practical tools for bioimaging applications. Carbon monoxide (CO) is a key gaseous signal molecule and its imaging in living systems has attracted great attention in recent years. In this work, a very easy-to-get NIR fluorescent probe with a remarkable large pseudo-Stokes shift (238 nm) for detection of CO was reported. This probe was found to show a rapid NIR fluorescent turn-on response for CO with high selectivity, high sensitivity and a low detection limit (38 nM). Moreover, imaging CO in living cells and animals with this probe was successfully applied with a high signal-to-noise ratio. The results indicate that this probe can be used as a new practical tool for imaging of endogenous CO in living systems.

Magnetic Semiconductor Gd-Doping CuS Nanoparticles as Activatable Nanoprobes for Bimodal Imaging and Targeted Photothermal Therapy of Gastric Tumors

Targeted delivery of enzyme-activatable probes into cancer cells to facilitate accurate imaging and on-demand photothermal therapy (PTT) of cancers with high spatiotemporal precision promises to advance cancer diagnosis and therapy. Here, we report a tumor-targeted and matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed by covalent modification of Gd-doping CuS micellar nanoparticles with cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays a high r1 relaxivity (∼60.0 mM-1 s-1 per Gd3+ at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold) in response to MMP-2, allowing high-spatial-resolution magnetic resonance imaging (MRI) and low-background fluorescence imaging of gastric tumors as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN has a high photothermal conversion efficiency (PCE, ∼70.1%) under 808 nm laser irradiation, endowing it with the ability to efficiently generate heat to kill tumor cells. We demonstrate that T-MAN can accumulate preferentially in gastric tumors (∼23.4% ID%/g at 12 h) after intravenous injection into mice, creating opportunities for fluorescence/MR bimodal imaging-guided PTT of subcutaneous and metastatic gastric tumors. For the first time, accurate detection and laser irradiation-initiated photothermal ablation of orthotopic gastric tumors in intraoperative mice was also achieved. This study highlights the versatility of using a combination of dual biomarker recognition (i.e., αvβ3 and MMP-2) and dual modality imaging (i.e., MRI and NIR fluorescence) to design tumor-targeting and activatable nanoprobes with improved selectivity for cancer theranostics in vivo.

A lysosome-targetable fluorescent probe for imaging ONOO− in living cells and animals

Peroxynitrite (ONOO−) is one of the most important reactive oxygen species (ROS) in living systems and its subcellular detection is very important. In this research, a lysosome-targetable fluorescent probe for detection of exogenous and endogenous peroxynitrite in living systems was developed. This probe exhibits not only fast (25 s), highly sensitive (detection limit = 16 nM), and highly selective red to near-infrared fluorescent turn-on responses for ONOO− in the solution, but also excellent imaging ability for ONOO− in living cells and animals with low cytotoxicity. Moreover, this probe is lysosome-targetable and can be used for imaging lysosomal ONOO− in living cells. Overall, this work provides a new powerful fluorescent turn-on probe for detection of lysosomal peroxynitrite in living systems.

Iminocoumarin-based red to near-infrared fluorescent turn-on probe with a large Stokes shift for imaging H2S in living cells and animals

The development of organic dye-based fluorescent probes for detection of H2S in living systems has attracted considerable attention in recent years. In this work, a novel tetrahydroquinoxaline iminocoumarin-based red to near-infrared (red-to-NIR) fluorescent probe was developed for detection of H2S. This probe shows a rapid and distinct red-to-NIR fluorescent turn-on detection process for H2S with high selectivity and sensitivity (the detection limit was determined to be as low as 10 nM at physiological pH). In addition, this probe exhibits a remarkable large Stokes shift (128 nm) and low cytotoxicity, and can be applied for imaging H2S in living cells and animals. All these results demonstrated that this new probe is promising for detection of H2S both in vitro and in vivo.

A dual colorimetric and near-infrared fluorescent turn-on probe for Hg2+ detection and its applications

The increasing Hg2+ contamination in environment and ecosystem has gained wide attention and thus demands for its facile and effective detection. In this study, we constructed a new fluorescent probe (E)-2-(2-(3-(1,3-dithian-2-yl)-4-hydroxystyryl)- 4H-chromen-4-ylidene)malononitrile (DCM-Hg) for Hg2+ detection by incorporating the 1, 3-dithiane group to the dicyanomethylene-4H-pyran fluorophore for the first time. This probe can selectively detect Hg2+via the Hg2+-triggered deprotection reaction of thioacetals, which leads to a distinct color change from purple to pink and obvious fluorescence enhancement in the near-infrared (NIR) region. The NIR fluorescence intensity increased linearly with Hg2+ level within the range from 0 to 100 μM and the detection limit of DCM-Hg for Hg2+ was found to be 6.8 × 10−8 mol/L. Moreover, the probe could sense Hg2+ on paper strips and image Hg2+ in living cells with low cytotoxicity, which demonstrates its potential application in environment and biological science.

A distinctive near-infrared fluorescence turn-on probe for rapid, sensitive and chromogenic detection of sulfite in food

Sodium sulfite (Na2SO3) is widely used as a food additive, but the excessive residue of SO32− in food can cause irritative effects and damages to the human body. In this study, we reported a novel near-infrared (NIR) fluorescent probe (DCMQ) for visual detection of SO32− based on a chromogenic reaction. The probe can quantitatively determine SO32− with high specificity and sensitivity, fast response (<50 s) as well as a low detection limit (31.6 nM). A 1,4-Michael addition reaction was proposed for the sensing mechanism of this probe, which was confirmed by 1H NMR and HR-MS spectra. The probe has been successfully utilized to determine SO32− in food with good recovery, remarkable chromogenic effect and NIR fluorescence turn-on response. Furthermore, the probe has been prepared as a reagent kit for instant on-site visual detection of SO32− in food. Therefore, this probe has great potential application for the detection of SO32− in food.