Guangle Niu

A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation

Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen (1O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of 1O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility.

Coumarin- and rhodamine-fused deep red fluorescent dyes: synthesis, photophysical properties, and bioimaging in vitro.

A series of deep red fluorescent dyes (CR1 to CR3) was developed via introduction of a coumarin moiety into the rhodamine molecular skeleton. The novel dyes possessed the individual advantages of coumarin and rhodamine derivatives, and the emission wavelength was extended to the deep red region (>650 nm) due to the extension of fused-ring conjugate structure simultaneously. To illustrate its value, we designed and conveniently synthesized a series of novel deep red bioimaging dyes (CR1E to CR3E) by esterification of CR1 to CR3, which could selectively stain mitochondria. They were superior to the MitoTrackers for mitochondrial staining in terms of large Stokes shift, excellent contrast for imaging, high photostability, and low cytotoxicity. Furthermore, the fluorescence of the coumarin moiety and rhodamine-like fluorophore could be switched like classical rhodamine. Thus, they could be used as an effective platform in constructing fluorescence sensors. Based on this fact, we constructed a novel ratiometric sensor (CR1S) for Hg(2+) with good selectivity that could be successfully applied to the imaging of Hg(2+) in living A549 cells. This design strategy is straightforward and adaptable to various deep red dyes and sensing platforms by simply introducing different fluorophores.

Near-Infrared Probe Based on Rhodamine Derivative for Highly Sensitive and Selective Lysosomal pH Tracking

The development of near-infrared fluorescent probes with low pKa, high selectivity, high photostability, and high sensitivity for lysosomal pH detection is of great importance. In the present work, we developed a novel near-infrared lysosomal pH probe (Lyso-hNR) based on a rhodamine derivative. Lyso-hNR showed fast, highly sensitive, and highly selective fluorescence response to acidic pH caused by the H+-induced structure changes from the nonfluorescent spirolactam form to the highly emissive open-ring form. Lyso-hNR displays a significant fluorescence enhancement at 650 nm (over 280-fold) from pH 7.0 to 4.0 with a pKa value of 5.04. Live cell imaging data revealed that Lyso-hNR can selectively monitor lysosomal pH changes with excellent photostability and low cytotoxicity. In addition, Lyso-hNR can be successfully used in tracking lysosomal pH changes induced by chloroquine and those during apoptosis. All these features render Lyso-hNR a promising candidate to investigate lysosome-associated physiological and pathological processes.

Aminobenzofuran-Fused Rhodamine Dyes with Deep-Red to Near-Infrared Emission for Biological Applications

Aminobenzofuran-fused rhodamine dyes (AFR dyes) containing an amino group were constructed by an efficient condensation based on 3-coumaranone derivatives. AFR dyes exhibited significantly improved properties, including deep-red and near-infrared emissions, a large Stokes shift, good photostability, and wide pH stability. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium assay experiments show that these AFR dyes are biocompatible for their low cytotoxicity to both A549 and HeLa cells. Cell imaging data reveal that AFR1, AFR1E, and AFR2 are mainly located in the mitochondria, while AFR3 is a lysosome tracker. As far as we know, NIR AFR3 is the longest fluorescent rhodamine derivative containing the amino group. These amino group-containing AFR dyes hold great potential in fluorogenic detection, biomolecule labeling, and cell imaging.

Deep-Red Emissive Crescent-Shaped Fluorescent Dyes: Substituent Effect on Live Cell Imaging

A series of crescent-shaped fluorescent dyes (CP1-CP6) were synthesized by hybridizing coumarin and pyronin moieties with different amino substituents at both ends. The molecular structures and photophysical properties of these fluorescent dyes were investigated through X-ray diffraction, absorption spectroscopy, and fluorescence spectroscopy. Results show that the fluorescent dyes exhibited crescent-shaped structures, deep-red emissions (approximately 650 nm), and significant Stokes shifts. In live-cell-imaging experiments, CP1 stains mitochondria, whereas CP3 and CP6 stain the lysosomes in a cytoplasm and the RNA in nucleoli. The relationships between different amino substituent groups and the imaging properties of CP dyes were discussed as well. Additionally, findings from the cytotoxicity and photostability experiments on living cells indicated the favorable biocompatibility and high photostability of the CP dyes.

Deep-Red and Near-Infrared Xanthene Dyes for Rapid Live Cell Imaging.

In this work, two xanthene dyes (H-hNR and TF-hNR) have been synthesized by a convenient and efficient method. These two dyes exhibited deep-red and near-infrared emissions, high fluorescence quantum yields, and good photostability. Their structure-optical properties were investigated by X-ray crystal structure analysis and density functional theory calculations. Live cell imaging data revealed that H-hNR and TF-hNR could rapidly stain both A549 and HeLa cells with low concentrations. The excellent photophysical and imaging properties render them as promising candidates for use in live cell imaging.

Two-photon-excited near-infrared emissive carbon dots as multifunctional agents for fluorescence imaging and photothermal therapy

C dots (CDs) have shown great potential in bioimaging and phototherapy. However, it is challenging to manipulate their fluorescent properties and therapeutic efficacy to satisfy the requirements for clinic applications. In this study, we prepared S, Se-codoped CDs via a hydrothermal method and demonstrated that the doping resulted in excitation wavelength-independent near-infrared (NIR) emissions of the CDs, with peaks at 731 and 820 nm. Significantly, the CDs exhibited a photothermal conversion efficiency of ~58.2%, which is the highest reported value for C nanostructures and is comparable to that of Au nanostructures. Moreover, the CDs had a large two-photon absorption cross section (~30,045 GM), which allowed NIR emissions and the photothermal conversion of the CDs through the two-photon excitation (TPE) mechanism. In vitro and in vivo tests suggested that CDs can function as new multifunctional phototheranostic agents for the TPE fluorescence imaging and photothermal therapy of cancer cells.

Water-Soluble Polythiophene for Two-Photon Excitation Fluorescence Imaging and Photodynamic Therapy of Cancer

Positively charged water-soluble polythiophene (PT0) that could self-assemble into nanoparticles in pure water solution was designed and synthesized. PT0 exhibited high photostabilities and pH stabilities, excellent biocompatibility, strong 1O2 generation capability, and large two-photon absorption cross sections. Moreover, we showed that the fluorescence of PT0 was unaffected by the interference of biomolecules and metal ions. As an example application, PT0 was demonstrated to be capable of simultaneous cell imaging and photodynamic therapy under either one-photon or two-photon excitation modes.

Keto-benzo[h]-Coumarin-Based Near-Infrared Dyes with Large Stokes Shifts for Bioimaging Applications.

Fluorescence imaging is a promising tool for the visualization of biomolecules in living systems and there is great demand for new fluorescent dyes that absorb and emit in the near-infrared (NIR) region. Herein, we constructed three new fluorescent dyes (NBC dyes) based on keto-benzo[h]coumarin (k-BC) and benzopyrilium salts. These dyes showed large Stokes shifts (>100 nm) and NIR emission (>800 nm). The relationship between the structures and optical properties of these dyes was further investigated by using density functional theory calculations at the B3LYP/6-3G level of theory. Fluorescence images indicated that the fabricated dyes exhibited good photostability and low cytotoxicity and, thus, have potential applications as imaging agents in living cells and animals.

Coumarin-Based Boron Complexes with Aggregation-Induced Emission

Two coumarin-based boron complexes (HBN and MBN) with aggregation-induced emission were designed and synthesized. The photophysical properties of the complexes were investigated in different solvents and in the solid state. Results showed that the inhibited C═N isomerization by N,O-chelated BF2 caused the significant enhancement of fluorescence in THF. In particular, the complexes displayed red-shifted emissions (>60 nm) in mixed solvents of CH3CN and water because of the aggregation-induced charge-transfer enhancement. In the solid state, the bright red emission appeared at 650 nm (620 nm), with a Stokes shift of 170 nm. Cell-imaging experiments indicated that the complexes have good membrane permeability and can be used as lysosome trackers.