Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models.

Hydrogen peroxide (H2O2) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H2O2 in multiple diseases, such as PM2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H2O2) by introducing pentafluorobenzenesulfonyl as a H2O2 sensing unit into the NIR hemicyanine platform. HCy-H2O2 exhibits good sensitivity and selectivity toward H2O2, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H2O2 has stable mitochondria-targetable ability and permits monitoring of the up-generated H2O2 level during mitophagy. Furthermore, using HCy-H2O2, we have successfully observed an overproduced mitochondrial H2O2 in ambient PM2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H2O2 has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H2O2 a promising tool for cancer diagnosis and imaging-guided surgery.

Novel ratiometric fluorescent probe with large Stokes shift for selective sensing and imaging of Zn2+ in live cell.

A novel ratiometric fluorescent probe, namely 5-[(3-dicyanoylidene -5.5-dimethyl) cyclohexenyl-1-ethenyl] salicylaldehyde-3'-hydroxybenzohydrazone (DCSH) is presented for the selective sensing of Zn2+ ion in acetonitrile/water (2/3, pH 7.4) solution. Introducing Zn2+ ions notably caused the peak emission of DCSH to shift from 560 nm to 646 nm, accompanied with a significant enhancement of its intensity. A vivid change in fluorescence color from yellow to red facilitated the immediate identification of Zn2+ ions by visual observation. DCSH exhibits substantial Stokes shifts (110 and 196 nm), rapid detection capability (within 10 s) and high sensitivity to Zn2+ ions, achieving a limit of detection of 31.2 nM. The response mechanism is supposed to involve the block of C = N bond isomerization and excited state intramolecular proton transfer (ESIPT) along with the enhancement of fluorescence through chelation (CHEF) effect. DCSH was effectively utilized for ratiometric fluorescence imaging to monitor exogenous Zn2+ concentrations in HeLa cells. Significantly, DCSH is capable of monitoring elevated levels of Zn2+ ion during apoptosis induced by L-Buthionine sulfoximine (BSO).

Bovine Serum Albumin Template-Mediated Fabrication of Ruthenium Dioxide/Multiwalled Carbon Nanotubes: High-Performance Electrochemical Dopamine Biosensing in Human Serum.

The presence of abnormal dopamine (DA) levels may cause serious neurological disorders, therefore, the quantitative analysis of DA and its related research are of great significance for ensuring health. Herein, the bovine serum albumin (BSA) template method has been proposed for the preparation of catalytically high-performance ruthenium dioxide/multiwalled carbon nanotube (RuO2/MWCNT) nanocomposites. The incorporation of MWCNTs has improved the active surface area and conductivity while effectively preventing the aggregation of RuO2 nanoparticles. The outstanding electrocatalytic performance of RuO2/MWCNTs has promoted the electro-oxidation of DA at neutral pH. The electrochemical sensing platform based on RuO2/MWCNTs has demonstrated a wide linear range (0.5 to 111.1 µM), low detection limit (0.167 µM), excellent selectivity, long-term stability, and good reproducibility for DA detection. The satisfactory recovery range of 94.7% to 103% exhibited by the proposed sensing podium in serum samples signifies its potential for analytical applications. The aforementioned results reveal that RuO2/MWCNT nanostructures hold promising aptitude in the electrochemical sensor to detect DA in real samples, further offering broad prospects in clinical and medical diagnosis.

Bridging biological and food monitoring: A colorimetric and fluorescent dual-mode sensor based on N-doped carbon dots for detection of pH and histamine.

Rapid and sensitive monitoring of pH and histamine is crucial for bridging biological and food systems and identifying corresponding abnormal situations. Herein, N-doped carbon dots (CDs) are fabricated by a hydrothermal method employing dipicolinic acid and o-phenylenediamine as precursors. The CDs exhibit colorimetric and fluorescent dual-mode responses to track pH and histamine variations in living cells and food freshness, respectively. The aggregation-induced emission enhancement and intramolecular charge transfer result in a decrease in absorbance and an increase in fluorescence, which become readily apparent as the pH changes from acidic to neutral. This property enables precise differentiation between normal and cancerous cells. Furthermore, given the intrinsic basicity of histamine, pH-responsive CDs are advantageous for additional colorimetric and fluorescent monitoring of histamine in food freshness, achieving linearities of 25-1000 µM and 30-1000 µM, respectively, which are broader than those of alternative nanoprobes. Interestingly, the smartphone-integrated sensing platform can portably and visually evaluate pH and histamine changes due to sensitive color changes. Therefore, the sensor not only establishes a dynamic connection between pH and histamine for the purposes of biological and food monitoring, but also presents a novel approach for developing a multifunctional biosensor that can accomplish environmental monitoring and biosensing simultaneously.

Hydrophobic carbon quantum dots with red fluorescence: An optical dual-mode and smartphone imaging sensor for identifying Chinese Baijiu quality.

Chinese Baijiu (Liquor) is a popular alcoholic beverage, and the ethanol content in Baijiu is closely related to its quality; therefore, it is of great significance to explore a facile, sensitive, and rapid method to detect ethanol content in Baijiu. Hydrophobic carbon quantum dots (H-CQDs) with bright red fluorescence (24.14 %) were fabricated by hydrothermal method using o-phenylenediamine, p-aminobenzoic acid, manganese chloride, and hydrochloric acid as reaction precursors. After the introduction of ultrapure water into the ethanol solution dissolved with H-CQDs, the aggregated H-CQDs resulted in significant changes in fluorescence intensity and absorbance. On this basis, a sensor for detecting ethanol by optical dual-mode and smartphone imaging was constructed. More importantly, the sensor can be used for detecting ethanol content in Chinese Baijiu with satisfactory results. This sensing platform has great potential for quality identification in Chinese Baijiu, broadening the application scope of CQDs in food safety detection.

Visualization of polarity changes in endoplasmic reticulum (ER) autophagy and rheumatoid arthritis mice with near-infrared ER-targeted fluorescent probe.

The crucial cellular activities for maintaining normal cell functions heavily rely on the polarity of the endoplasmic reticulum (ER). Understanding how the polarity shifts, particularly in the context of ER autophagy (ER-phagy), holds significant promise for advancing knowledge of disorders associated with ER stress. Herein, a polarity-sensitive fluorescent probe CDI was easily synthesized from the condensation reaction of coumarin and dicyanoisophorone. CDI was composed of coumarin as the electron-donating moiety (D), ethylene and phenyl ring as the π-conjugation bridge, and malononitrile as the electron-accepting moiety (A), forming a typical D-π-A molecular configuration that recognition in the near-infrared (NIR) region. The findings suggested that as the polarity increased, the fluorescence intensity of CDI decreased, and it was accompanied by a redshift of emission wavelength at the excitation wavelength of 524 nm, shifting from 641 nm to 721 nm. Significantly, CDI exhibited a notable ability to effectively target ER and enabled real-time monitoring of ER-phagy induced by starvation or drugs. Most importantly, alterations in polarity can be discerned through in vivo imaging in mice model of rheumatoid arthritis (RA). CDI has been proven effective in evaluating the therapeutic efficacy of drugs for RA. ER fluorescent probe CDI can be optically activated in lysosomes, providing a sensitive tool for studying ER-phagy in biology and diseases.

A novel pH-sensitive hemi-cyanine containing tetrahydropyridine ring near-infrared fluorescence probe with lysosome-targeting ability.

In recent years, hemi-cyanine dyes have been widely used as biological probes due to their red-light emission characteristics and high fluorescence quantum yield. In this study, we synthesized a novel hemi-cyanine dye containing a tetrahydropyridine ring. A lysosomal target was introduced into its structure to create a new pH-sensitive near-infrared fluorescent probe that successfully targeted lysosomes. The results showed that when the probe solution was excited at the absorption wavelength of 650 nm, its fluorescence emission wavelength was about 700 nm, and the peak intensity changed with different pH values in a wide range. Therefore, this probe enabled non-invasive detection of changes in the acidic environment of lysosomes in living organisms and showed good imaging capabilities. Moreover, the probe displays high sensitivity and good stability. The theoretical calculation of a probe structure has also been completed to discuss the relationship between structure and property.

A specific dual-locked fluorescence probe to visualize the dynamic changes of lipid droplets and hypochlorous acid in inflammation.

Inflammation is a key factor leading to the occurrence and development of many diseases, both lipid droplets (LDs) and hypochlorous acid (HClO/ClO-) are regarded as the important biomarkers of inflammation. Therefore, it is of great significance to develop an efficient single chemical sensor that can simultaneously detect these two biomarkers. To achieve the goal, we developed a dual-locked fluorescence probe (TPA-DNP) by fusing two targets activated reporting system, its implementation was achieved by turning-on the fluorescence of TPA-DNP through LDs and HClO/ClO- simultaneously. In simulated LDs environment, TPA-DNP displayed excellent selectivity to HClO/ClO-, high sensitivity (LOD = 0.527 µM) and strong anti-interference ability. In addition, cell and zebrafish imaging experiments showed that TPA-DNP could be utilized to visualize exogenous/endogenous HClO/ClO- in LDs environment, and could also be used to observe the impact of LDs changes on the HClO/ClO- detection. On the basis, TPA-DNP served as a favorable tool to achieve visualization of inflammatory dynamic changes.

Design of a dual-mode ratiometric fluorescent probe via MOF-on-MOF strategy for Al (III) and pH detection.

BACKGROUND: The construction of ratiometric fluorescent MOF sensors with integrated self-calibration and dual-channel detection can efficiently overcome the deficiencies of single-signal sensing. In this regard, the rational design of structurally functionalized MOFs is paramount for enhancing their performance in ratiometric fluorescent sensors. Lately, the concept of MOF-on-MOF design has garnered notable interest as a potential strategy for regulating the structural parameters of MOFs by integrating two or more distinct MOF types. Great efforts have been dedicated to exploring new MOF-on-MOF hybrids and developing their applications in diverse fields. Even so, these materials are still in the stage of advancement in the sensing field. RESULTS: Herein, a Zr-based metal-organic framework anchored on a rare-earth metal-organic framework (UiO-66(OH)2@Y-TCPP) was prepared for the ratiometric fluorescence detection toward Al (III) and pH. In this probe, the UiO-66(OH)2 featured hydroxyl active sites for Al (III), leading to a significant enhancement in fluorescence intensity upon the addition of Al (III), while the signal emitted by the red-emitting Y-TCPP, serving as the reference, remained constant. UiO-66(OH)2@Y-TCPP exhibited excellent selectivity for Al (III) sensing with a wider linear range of 0.1-1000 µM, and a lower detection limit of 0.06 µM. This probe has also been utilized for the quantitative determination of Al (III) in hydrotalcite chewable tablets with satisfactory results. In addition, the probe realized ratiometric pH sensing in the range of 7-13 using UiO-66(OH)2 as an interior reference. The paper-based probe strip was developed for visual pH sensing. By installing color recognition and processing software on a smartphone, real-time and convenient pH sensing could be achieved. SIGNIFICANCE: This is the first ratiometric fluorescent sensor for Al (III) and pH detection based on a MOF-on-MOF composite probe, which yields two different response modes. The detection results of Al (III) in hydrotalcite chewable tables and smartphone imaging for pH test paper demonstrate the practicability of the probe. This work opens up a new outlook on constructing a multi-functional application platform with substantial potential for employment in environmental and biological analysis tasks.

Aptamer-Modified Tetrahedral DNA Nanostructures as Drug Delivery System for Cancer Targeted Therapy.

Improving the selective delivery and uptake efficiency of chemotherapeutic drugs remains a challenge for cancer-targeted therapy. In this work, a DNA tetrahedron is constructed as a targeted drug delivery system for efficient delivery of doxorubicin (Dox) into cancer cells. The DNA tetrahedron is composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which can target the nucleolin protein on the cell membrane of cancer cells. The prepared DNA tetrahedron has a high drug-loading capacity and demonstrates pH-responsive Dox release properties. This enables efficient delivery of Dox into targeted cancer cells while reducing side effects on nontarget cells. The proposed drug delivery system exhibits significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provides a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.

A sensitive "turn-on" Schiff-base fluorescent probe for the selective detection of Fe3+ and bio-imaging.

A novel Schiff-base fluorescent probe, 4-(N-(2- hydroxyl-1-naphthalymethylimino)-ethylamino) -7-nitro-1,2,3-benzoxadiazole (HENB) was synthesized and utilized for spectral sensing of Fe3+ ions at neutral pH. The binding of Fe3+ to HENB in C2H5OH-HEPES buffer (1:1 v/ v, 25 mM, pH 7.2) resulted in a pronounced emission enhancement at 530 nm, which is possibly due to the inhibition of photo-induced electron transfer (PET) process as well as the chelation enhanced fluorescence (CHEF) effect. HENB shows good selectivity and sensitivity toward Fe3+ with the detection limit as low as 4.51 nM. Test strips made of HENB was used for rapid "naked-eye" detection of Fe3+ ions in aqueous medium. Moreover, HENB was successfully applied in fluorescence imaging of exogenous and endogenous Fe3+ in live Hela cells as well as zebrafish. Importantly, HENB is capable of effectively monitoring the variations of Fe3+ in living cells during ferroptosis process.

A novel multi-functional fluorescent probe for dual-channel detection of SO2 and Hg2+ and dynamic visualization of SO2 fluctuations in vivo upon mercury exposure.

Although there are many drugs used for the treatment of mercury poisoning, it is remains confused that pathological symptoms associated with Hg2+-induced oxidative stress. It is reported that SO2 can be generated as the anti-oxidant, and plays an important role in maintaining redox balance in cells. There has not yet been a study to precisely track the changes in SO2 during mercury ion poisoning. We developed a novel dual-response fluorescence probe (CY-SPH) for respective or successive determination of Hg2+ and SO2 in neutral aqueous media. The nucleophilic addition of HSO3- toward CY-SPH caused a significant fluorescence enhancement at 455 nm while the Hg2+ -triggered desulfurization of CY-SPH to the final phenolic product (CY-OH) elicited a markedly enhanced emission at 760 nm, allowing for two-color visualization of Hg2+ and SO2 with good selectivity (detection limit: 67.2 nM for Hg2+ and 34.7 nM for SO2). Moreover, CY-OH could undergo further nucleophilic addition reaction with HSO3- and resulted in a decrease in emission at 760 nm and an increase in emission at 438 nm, enabling the ratiometric determination of SO2 with better sensitivity (detection limit, 3.50 nM). Significantly, CY-SPH can monitor the endogenous SO2 fluctuations upon mercury exposure by means of confocal fluorescence imaging, which may prove valuable for deciphering the relationship between SO2 levels and the mercury induced oxidative stress. We anticipated that this research will promote to understand the functions of SO2 under the oxidative stress by Hg2+.

Drug-Primed Self-Assembly of Platinum-Single-Atom Nanozyme to Regulate Cellular Redox Homeostasis Against Cancer.

Single-atom nanozymes (SAzymes) with high catalytic activity exhibit the potential to disequilibrate the reactive oxygen metabolic balance in the tumor microenvironment (TME), which contains several endogenous reductive substances such as glutathione (GSH). Herein, a novel nano-assembly (CDs@Pt SAs/NCs@DOX) is first constructed using drug-primed platinum (Pt) single-atom or nanocluster nanozymes with a Pt loading of 34.8%, which exhibits prominent dual enzymatic activities to mimic peroxidase (POD) and glutathione oxidase (GSHOx). The unique GSHOx-like activity can efficiently scavenge GSH with a relatively low Km (1.04 mm) and high Vmax (7.46 × 10-6  m s-1 ), thus avoiding single oxygen (1 O2 ) depletion. CDs@Pt SAs/NCs@DOX simultaneously demonstrates low-temperature photothermal therapy and TME- or laser-controlled disassembly and drug release, which can effectively regulate cellular redox homeostasis and achieve high tumor growth inhibition. These outcomes may provide promising strategies for the preparation of Pt SAzymes with multiple activities and variable-sized nano-assemblies, allowing for broader applications of SAzymes and nano-assemblies in the biomedical field.

Ultrasensitive Electrochemical Platform for Dopamine Detection Based on CoNi-MOF@ERGO Composite.

An electrochemical sensor applied for dopamine (DA) detection was constructed. An easy static way was used to synthesize bimetallic CoNi-MOF. Next, it was mixed with graphene oxide (GO) under ultrasound to get a uniform suspension. Subsequently, the solution was coated on the glassy carbon electrode (GCE) to form CoNi-MOF@ERGO/GCE by the electrochemical reduction method. The interaction between CoNi-MOF and electrochemically reduced graphene oxide (ERGO) enhances the electrocatalytic performance for DA detection. CoNi-MOF@ERGO/GCE has a wider linear range (0.1-400 µM) and a lower detection limit (0.086 µM) under optimum conditions. Furthermore, it has been applied to test DA in human serum samples. The results reveal that the DA sensor shows excellent performance, which will provide a novel idea for more sensitive and quicker DA detection.

Recent advances in fluorescent probes for dual-detecting ONOO- and analytes.

Although peroxynitrite (ONOO-) plays an essential role in cellular redox homeostasis, its excess ONOO- will affect the normal physiological function of cells. Therefore, real-time monitoring of changes in local ONOO- will contribute to further revealing the biological functions. Reliable and accurate detection of biogenic ONOO- will definitely benefit for disentangling its complex functions in living systems. In the past few years, more fluorescent probes have been developed to help understand and reveal cellular ONOO- changes. However, there has been no comprehensive and critical review of multifunctional fluorescent probes for cellular ONOO- and other analytes. To highlight the recent advances, this review first summarized the recent progress of multifunctional fluorescent probes since 2018, focusing on molecular structures, response mechanisms, optical properties, and biological imaging in the detection and imaging of cellular ONOO- and analytes. We classified and discussed in detail the limitations of existing multifunctional probes, and proposed new ideas to overcome these limitations. Finally, the challenges and future development trends of ONOO- fluorescence probes were discussed. We hoped this review will provide new research directions for developing of multifunctional fluorescent probes and contribute to the early diagnosis and treatment of diseases.

Artificial intelligence-integrated smartphone-based handheld detection of fluoride ion by Al3+-triggered aggregation-induced red-emssion enhanced carbon dots.

Artificial intelligence (AI)-integrated smartphone-based handheld determination platform, based on 3D printed accessory, Al3+-triggered aggregation-induced red-emssion enhanced carbon dots (CDs) test strip, and smartphone with self-developed YOLO v3 AI algorithm-based application, proves the feasibility for intelligent real-time on-site quantitation of F- through tracking a consecutive fluorescence (FL) colour change. CDs, manifesting dual emission of moderate green emission at 512 nm and weak red one at 620 nm under 365 nm excitation, were synthesized hydrothermally from alizarin carmine and citric acid. CDs@Al3+, with distinct aggregation-induced red-emssion enhancement and green-emssion quenchment, were prepared by adding Al3+ to the CDs solution. Inspiringly, due to intrinsic ratiometric FL variation (I620/I512), CDs@Al3+ engender a successive FL colour variation from red to green in response to different concentrations of F- with low limit of detection of 7.998 µM and wide linear range of 150-1200 µM based on excellent linearity correlation between R/G value and F- concentration. Furthermore, F- content in tap water, toothpaste and milk could be intelligently, speedily, and straightforwardly analyzed through the AI-integrated smartphone-based handheld detection platform. It is fervently desired that our study will motivate a brand-new perspective for the promotion of efficacious detection strategy and the extension of practical application promise.

Rational Design of Orange-Red Emissive Carbon Dots for Tracing Lysosomal Viscosity Dynamics in Living Cells and Zebrafish.

Lysosomal viscosity is an essential microenvironment parameter in lysosomes, which is closely associated to the occurrence and development of various diseases, including cancer. Thus, accurately quantifying lysosomal viscosity changes is highly desirable for a better understanding of the dynamics and biological functions of lysosomes. In this study, lysosome self-targetable orange-red emissive carbon dots (OR-CDs) were rationally designed and developed for monitoring lysosomal viscosity fluctuations. The enhanced fluorescence of OR-CDs could be obviously observed as the viscosity increased from 1.07 to 950 cP. Moreover, the as-prepared OR-CDs could quickly enter cells for lysosome-targeting imaging and visualize viscosity variations in living cells and zebrafish. More importantly, by utilizing OR-CDs, we successfully achieved tracing the variations in lysosomal viscosity during the autophagy process. Additionally, as cancer cells possess high viscosity than normal cells, the OR-CDs have been effectively utilized for cancer imaging from cell, tissue, and organ to in vivo levels. It is expected that the developed OR-CDs not only provide a meaningful tool for visualizing investigations of lysosome viscosity-related diseases but also shed light on the development based on the nanomaterial for the clinical diagnosis of cancer.

Engineering a gold nanoparticles-carbon dots nanocomposite with pH-flexibility for monitoring hydrogen peroxide released from living cells.

Constructing nanozymes with satisfactory catalytic efficiency under physiological conditions is still in great demand for facilitating the advancement of biocatalysts. We herein present a gold nanoparticles-carbon dots nanocomposite (Au-CDs) as an efficient photo-activated nanozyme for monitoring H2O2 released from living cells. The integration of CDs with AuNPs remarkably accelerates the catalytic activity at neutral pH via engaging Mn3+ ions as the mediators. Meanwhile, the reserved cyclodextrin cavities also enhance the adsorption capacity towards chromogenic substrates through host-guest interactions. Moreover, taking advantage of the inhibitory effect of H2O2 on the photo-oxidation ability of the Au-CDs nanocomposite, the Au-CDs based colorimetric method was able to realize in situ assessment of the hydrogen peroxide (H2O2) released from living cells. This method paves a new way to establish a promising biosensing platform for unraveling biological events.

Mitochondria-Targeting Multifunctional Fluorescent Probe toward Polarity, Viscosity, and ONOO- and Cell Imaging.

Abnormal changes occurring in the mitochondrial microenvironment are important markers indicating mitochondrial and cell dysfunction. Herein, we designed and synthesized a multifunctional fluorescent probe DPB that responds to polarity, viscosity, and peroxynitrite (ONOO-). DPB is composed of an electron donor (diethylamine group) and electron acceptor (coumarin, pyridine cations, and phenylboronic acid esters), in which the pyridine group with a positive charge is responsible for targeting to mitochondria. D-π-A structure with strong intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) properties give rise to respond to polarity and viscosity. The introduction of cyanogroup and phenylboronic acid esters increases the electrophilicity of the probe, which is prone to oxidation triggered by ONOO-. The integrated architecture satisfies the multiple response requirements. As the polarity increases, the fluorescence intensity of probe DPB at 470 nm is quenched by 97%. At 658 nm, the fluorescence intensity of DPB increases with viscosity and decreases with the concentration of ONOO-. Furthermore, the probe is not only successfully used to monitor mitochondrial polarity, viscosity, and endogenous/exogenous ONOO- level fluctuations but also to distinguish cancer cells from normal cells by multiple parameters. Therefore, as-prepared probe provides a reliable tool for better understanding of the mitochondrial microenvironment and also a potential approach for the diagnosis of disease.

Synthesis of a Red-Emitting Polarity-Sensitive Fluorescent Probe Based on ICT and Visualization for Lipid Droplet Dynamic Processes.

Abnormal lipid droplets (LDs) have been recognized as critical factors in many diseases because they are metabolically active and dynamic organelles. Visualization for LD dynamic processes is fundamental for elucidating the relationship of LDs and related diseases. Herein, a red-emitting polarity-sensitive fluorescent probe (TPA-CYP) based on intramolecular charge transfer (ICT) was proposed, which was constructed by employing triphenylamine (TPA) and 2-(5,5-dimethyl-2-cyclohex-1-ylidene)propanedinitrile (CYP) as electron donor and acceptor moiety, respectively. The spectra results underlined the excellent characteristics of TPA-CYP, such as high polarity sensitivity (Δf = 0.209 to 0.312), strong solvatochromic effect (λem 595-699 nm), and the large Stokes shifts (174 nm). Moreover, TPA-CYP exhibited a specific ability to target LDs and effectively differentiated cancer cells and normal cells. Surprisingly, TPA-CYP had been successfully applied to dynamic tracking of LDs, not only in inflammation induced by lipopolysaccharide (LPS), the process of oxidative stress, but also in live zebrafish. We believe that TPA-CYP could serve as a powerful tool to gain insight into the dynamics of LDs and to understand and diagnose LD-associated diseases.