Jie Niu

A mitochondria-targetable fluorescent probe with a large Stokes shift for detecting hydrogen peroxide in aqueous solution and living cells

Fluorescent probes with large Stokes shifts play a key role in maintaining the accuracy of biological imaging and minimizing the self-quenching effect. In this work, we have developed a novel fluorescent probe CAI, which possessed a large Stokes shift in various solutions. We found that CAI was capable of detecting hydrogen peroxide (H2O2) in aqueous solution. Furthermore, probe CAI can sense exogenous and endogenous H2O2 in the mitochondria of living RAW 264.7 cells. In addition, probe CAI exhibited ideal properties such as excellent photostability, high sensitivity and selectivity. This fluorescent dye with a large Stokes shift was expected to have a more broad range of applications for developing various fluorescent probes with large Stokes shifts.

Ratiometric fluorescent probe with AIE property for monitoring endogenous hydrogen peroxide in macrophages and cancer cells

Hydrogen peroxide (H2O2) plays a key role in the progression of human illnesses, such as autoimmune and auto-inflammatory diseases, infectious diseases, diabetes, and cancer, etc. In this work, we have discribed a novel probe, TPE-TLE, which remarkably displayed AIE property and ratiometric fluorescence emission profiles in the presence of H2O2. This ratiometric fluorescent probe with AIE property exhibits outstanding features such as the well-resolved emission peaks, high sensitivity, high selectivity, low cytotoxicity, and good cell-membrane permeability. These excellent attributes enable us to demonstrate the ratiometric imaging of endogenously produced H2O2 in macrophages and cancer cells based on the novel ratiometric probe with AIE property for the first time. By comparing two kinds of cells, it is firstly found that cancer cells should contain much more endogenous H2O2 than macrophages. We expect that TPE-TLE will be useful fluorescent platform for the development of a variety of ratiometric fluorescent probes with AIE property to achieve unique biological applications.

Unique phenanthrenequinone imidazole-based fluorescent materials with aggregation-induced or two-photon emission

Very recently, aggregation-induced emission (AIE) and two-photon (TP) emission materials have attracted great attention owing to their widespread applications. Herein, interestingly, we described a unique single fluorophore core with different substituents that can show either outstanding AIE or TP fluorescence properties. The introduction of an electron donating unit such as a tertiary amine group on the phenanthrenequinone imidazole core afforded a novel AIE-based fluorescent material PIN. The optical studies of PIN revealed that appropriate structural modifications on the phenanthrenequinone imidazole core could result in AIE character. On the other hand, modification of an electron-withdrawing moiety such as an indolium moiety on the same phenanthrenequinone imidazole-core provided a new material PID, which exhibited favorable TP emission, indicating that phenanthrenequinone imidazole derivatives could be exploited as TP materials. Furthermore, we have demonstrated that the novel AIE or TP materials constructed herein can be successfully applied for sensing targets of interest in aqueous and biological settings owing to their highly desirable emission profiles. The intriguing finding that careful modification of the phenanthrenequinone imidazole scaffold could afford excellent AIE or TP materials may open a new avenue to engineer robust materials with diverse properties based on a versatile core for various applications.

An AIE + ESIPT ratiometric fluorescent probe for monitoring sulfur dioxide with distinct ratiometric fluorescence signals in mammalian cells, mouse embryonic fibroblast and zebrafish

Sulfur dioxide (SO2) is associated with serious diseases including lung cancer, cardiovascular diseases, and many neurological disorders. However, discrimination of the physiological and pathological functions of SO2 in different living systems is restricted by the lack of functional molecular tools. To address this critical challenge, herein, we have developed a novel ratiometric probe, TPE-TE, for monitoring SO2 with distinct ratiometric fluorescence signals in mammalian cells, mouse embryonic fibroblasts, and zebrafish via a combination of an ESIPT mechanism and the aggregate fluorescence method for the first time. The TPE-TE exhibits well-resolved emission peaks, high sensitivity, excellent selectivity, and low cytotoxicity. Moreover, this probe possesses higher sensitivity in an aqueous solution than the current probes. Taking advantage of these prominent features, we have achieved the detection of endogenous and exogenous SO2 with distinct ratiometric fluorescence signals in mammalian cells and mouse embryonic fibroblast. For the detection of endogenous SO2, probe-loaded HeLa cells exhibited stronger ratiometric fluorescence signals than HepG2 cells. For the detection of exogenous SO2, it was found that macrophage cells exhibited stronger ratiometric fluorescence signals than cancer cells for the first time. Interestingly, mouse embryonic fibroblasts incubated with this probe showed unique ratiometric imaging. Moreover, TPE-TE could be suitable for ratiometric SO2 imaging in living zebrafish.

Two-photon fluorescent probe for detecting cell membranal liquid-ordered phase by an aggregate fluorescence method

The cell membranal liquid-ordered (Lo) phase can control the structure and function of cell membranes. In this study, we have engineered a novel two-photon (TP) fluorescent probe, TP-HVC18, which remarkably displayed two different fluorescence emission profiles in the aggregate and solution states in distinct polar environments. In accordance with its aggregate fluorescence, TP-HVC18 also can emit a red fluorescence signal in Lo phase vesicles. Taking advantage of this unique feature, we have demonstrated that the new TP probe TP-HVC18 is suitable for imaging membranal Lo phase by an aggregate fluorescence method. Furthermore, the robust probe also exhibited uncontinuous red fluorescence distribution in the cell membranal Lo phase. Based on this intriguing character, we also successfully showed that the novel probe can be employed to exhibit uncontinuous distribution of cell membranal Lo phase by a 3D imaging technique. We expect that this aggregation-based fluorescent platform may be extended for the development of a wide variety of TP fluorescent probes for detecting several biological species.

Novel alkyl chain-based fluorescent probes with large Stokes shifts used for imaging the cell membrane and mitochondria in different living cell lines

Fluorescent dyes with large Stokes shifts play a key role in developing multi-purpose fluorescent probes for a wide variety of targets. In this study, we developed two novel alkyl chain-based fluorescent probes (CA-C12 and CA-C2) with large Stokes shifts. The alkyl chain length of the probes affect the membrane permeability, and hence both probes can be successfully applied for sensing the cell membrane and mitochondria in different living cell lines. Furthermore, the probes CA-C12 and CA-C2 exhibited large Stokes shifts and excellent photostability in the different cell lines. The fluorescent dyes with large Stokes shifts were expected to have broader applications for developing various fluorescent probes with excellent optical properties.

A ratiometric fluorescent composite nanomaterial for RNA detection based on graphene quantum dots and molecular probes

RNA plays a central role in controlling cellular functions. Research of the content and distribution of RNA in living cells is of great significance to both biochemistry and biomedicine. However, ratiometric fluorescent probes for the detection of RNA in the cytoplasm and nucleoli are still rarely reported. We herein present the first example of a novel ratiometric fluorescent composite nanomaterial by using graphene quantum dots (GQDs) and a fluorescent probe molecule for the sensitive and selective detection of RNA. HVC-6 was selected as the detection group. The fluorescence was excited at 365 nm and the fluorescence emission at 470 and 610 nm increased gradually with the addition of RNA. The fluorescence intensity ratio of I610/I470 displayed a linear response to RNA. Furthermore, the developed nanomaterial HVC-6@GQDs showed potential for utilization as a fluorescent RNA probe in living cells.

Simultaneous Imaging of Ribonucleic Acid and Hydrogen Sulfide in Living Systems with Distinct Fluorescence Signals Using a Single Fluorescent Probe

Abstract Ribonucleic acid (RNA) and hydrogen sulfide (H2S) are important genes and gaseous signal molecules in physiological environment. However, simultaneous investigation of distribution and interrelation of RNA and H2S in living systems is restricted by lack of functional molecular tools. To address this critical challenge, the development of TP‐MIVC is described as the first paradigm of the probes that can concurrently report ribonucleic acid and hydrogen sulfide with distinct fluorescence signals in the cancer cells, zebrafish, and living animals. The advantageous features of the probe include high stability, low background fluorescence, high sensitivity, and two‐photon imaging property. Significantly, regardless of normal mice or tumor mice, tumor tissues exhibit stronger fluorescence intensity than other organs. More interestingly, it is found that TP‐MIVC is capable of distinguishing normal mice and tumor mice by in vivo imaging. This study may open a new pathway for distinguishing malignant and benign tumor by fluorescence imaging of RNA.