An estradiol-functionalized red-emissive photosensitizer for enhanced and precise photodynamic therapy of breast cancers.

In this work, we developed a red-absorbing photosensitizer (NBS-ER) with specific targeting ability toward estrogen receptors (ER). NBS-ER could specifically bind the overexpressed ER in breast cancers to increase its accumulation, thereby amplifying the photodynamic therapeutic effect. With the aid of red fluorescence from NBS-ER, imaging-guided therapy could be achieved.

Three birds one stone: an enzyme-activatable theragnostic agent for fluorescence diagnosis, photodynamic and inhibitor therapies.

AX11890, an inhibitor of overexpressed enzyme, KIAA1363, in some breast cancers, was conjugated with a benzo[a]phenothiazinium photosensitizer to develop a tumor micro-environment-responsive photosensitizer NBS-L-AX. In normal cells, the special geometry of NBS-L-AX causes the fluorescence and photodynamic therapeutic (PDT) effect of NBS-L to be quenched. In cancer cells, when allowed to interact with the enzyme KIAA1363, the geometry of NBS-L-AX changes such that it becomes fluorescent and photodynamically active. Thus, the material of NBS-L-AX serves as an activated imaging and PDT treatment agent for breast cancers. In addition, NBS-L-AX also shows a selective inhibition effect against breast cancer cells.

Dual-ratiometric fluorescence sensing and real-time detection of HOCl and NQO1 using a single fluorescent probe under one-wavelength excitation.

Overexposure to hypochlorous acid (HOCl) can lead to cellular oxidative stress. In response to the stress, the body activates related factor that upregulates a potent antioxidant enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1). A method that can simultaneously detect HOCl and NQO1 can help to understand their interactions during homeostasis. However, the methods are still limited due to the complexity of the biological environment. In this work, we present for the first time a dual-ratiometric fluorescent probe (NH) that can distinguish between HOCl and NQO1. Probe NH had ratiometric fluorescence responses by changing from red (λmaxem = 643 nm) to green (λmaxem = 517 nm) in the presence of HOCl and from red to mixed blue (λmaxem = 483 nm)/red in the presence of NQO1 under single-wavelength excitation. This probe had high selectivity and sensitivity towards HOCl and NQO1 in vitro. Moreover, probe NH could specifically image exogenous or endogenous HOCl and NQO1 in living cells through different emission channels. This probe provides a practical tool for studying the correlation of HOCl and NQO1 in biological systems.

A ratiometric fluorescent probe with large Stokes shift and emission shift for sensing hydrazine in living organisms.

As a highly toxic reagent, hydrazine (N2H4) is notorious to human beings and the environment. To simply and conveniently detect N2H4 in environmental and biological systems, a ratiometric fluorescent probe MA-N2H4 was developed with excellent sensitivity and selectivity. Probe MA-N2H4 was readily prepared based on a naphthalene as the fluorescent scaffold and an indanedione group as the responsive moiety for N2H4. This probe displayed a red-emitting fluorescence at 670 nm with a large Stokes shift (200 nm). After treatment with N2H4, a significant blue-shifted emission at 440 nm could be observerd, which led to an extremely large emission wavelength shift (230 nm). The fluorescent intensity ratio (I440/I670) of probe MA-N2H4 was rapidly and significantly increased (273-fold) within 18 min. The detection limit for N2H4 was 0.5 µM. In addition, the probe was successfully employed for tracking N2H4 in living cells and zebrafish through a ratiometric manner.

A Ratiometric, Fast-Responsive, and Single-Wavelength Excited Fluorescent Probe for the Discrimination of Cys and Hcy.

The ratiometric detection of cysteine (Cys) and homocysteine (Hcy) is very challenging because of their highly similar chemical structures and properties. By introducing the phenylethynyl group into a coumarin dye as the sensing group, the ratiometric fluorescent probe CP was developed to selectively and rapidly discriminate between Cys and Hcy. With a single-wavelength excitation, the presence of Cys or Hcy induced the probe to produce distinct ratiometric fluorescence changes: from red (λmaxem = 608 nm) to blue (λmaxem = 485 nm) toward Cys and from red to mixed red/blue toward Hcy. Moreover, the probe was capable of visualizing and discriminating between intracellular Cys and Hcy in HeLa cells and zebrafish by exhibiting different ratiometric fluorescence signals.

An endoplasmic reticulum-targeting fluorescent probe for discriminatory detection of Cys, Hcy and GSH in living cells.

Endoplasmic reticulum, known to us as the ER, is the largest organelle in many kinds of eukaryotic cells and plays vital roles in maintaining the normal function of cells. Biothiols (Cys, Hcy, GSH) in secretory proteins will be modified as they enter the ER and are of great importance in balancing redox state of ER environments. In this article, we have developed the first endoplasmic reticulum-targeting fluorescent probe, ER-CP, for concurrent distinguishment of Cys, Hcy and GSH with favorable sensitivity and selectivity. ER-CP was successfully used in fluorescence imaging of Cys, Hcy and GSH in HeLa cells. In addition, ER-CP exhibited a good ER-targeting property (Pearson's correlation coefficient = 0.90).

A dual-ratiometric fluorescent probe for individual and continuous detection of H2S and HClO in living cells.

HClO and H2S are crucial for maintaining the homeostasis in cells and play vital roles in many physiological and pathological processes. Herein, we present a fluorescent probe that can respectively and simultaneously detect H2S and HClO in a dual-ratiometric manner with good linearity. Utilizing this probe, the imaging of intracellular H2S or/and HClO in living cells in a ratiometric manner was achieved.

Simultaneous detection of Cys/Hcy and H2S through distinct fluorescence channels.

Hydrogen sulfide (H2S), cysteine (Cys) and homocysteine (Hcy) play critical roles in human pathologies and there are close interconnections between them in their generation and metabolism in living systems. To elucidate their complex interplay networks, single-molecule fluorescent probes enabling simultaneous detection of H2S and Cys/Hcy from distinct emission channels have been becoming indispensable tools. In this report, we have rationally developed a novel fluorescent probe, NC, for H2S and Cys/Hcy by integrating an amino 7-nitro-1, 2, 3-benzoxadiazole (NBD) moiety and an azide group into the coumarin platform. NC exhibited good selectivity and sensitivity for the discriminatory detection of H2S and Cys/Hcy, and its capability for imaging of intracellular H2S and Cys/Hcy was proved.

A rapid and sensitive fluorescent probe for detecting hydrogen polysulfides in living cells and zebra fish.

Hydrogen polysulfides (H2Sn, n>1) plays crucial roles in many biological processes, while it remains a challenge for rapid and selective detection of H2Sn. We designed and synthesized a turn-on fluorescent probe (JCCF) for detecting H2Sn based on a new julolidine-coumarinocoumarin scaffold. H2Sn could trigger a dramatic fluorescence enhancement (52-fold) with a fast response time and a low detection limit of 98.3 nM (S/N = 3). Moreover, JCCF was successfully applied to image H2Sn in living cells and zebra fish with low cytotoxicity.

Simultaneous Detection of Glutathione and Hydrogen Polysulfides from Different Emission Channels.

Glutathione (GSH) and hydrogen polysulfides (H2Sn) play crucial roles in many physiological processes. To unravel the complicated interrelationship and cellular cross-talk between GSH and H2Sn, the development of single-molecule fluorescent probes that can selectively sense GSH and H2Sn simultaneously from different emission channels is highly desirable. In this report, we have developed the first dual-detection fluorescent probe, ACC-SePh, which responded to GSH with green fluorescence emission, whereas it reacted with H2Sn and emitted blue fluorescence. The probe exhibited excellent selectivity and sensitivity toward GSH and H2Sn over other common reactive sulfur species, such as Cys, Hcy and H2S. Importantly, we also demonstrated that ACC-SePh can be used for dual-channel imaging of endogenous GSH and H2Sn in living RAW264.7 cells.