Three-in-One: Molecular Engineering of D-A-π-A Featured Type I and Type II Near-Infrared AIE Photosensitizers for Efficient Photodynamic Cancer Therapy and Bacteria Killing.

Bacterial infections are closely correlated with the genesis and progression of cancer, and the elimination of cancer-related bacteria may improve the efficacy of cancer treatment. However, the combinatorial therapy that utilizes two or more chemodrugs will increase potential adverse effects. Image-guided photodynamic therapy is a highly precise and potential therapy to treat tumor and microbial infections. Herein, four donor-acceptor-π-bridge-acceptor (D-A-π-A) featured near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) (TQTPy, TPQTPy, TQTC, and TPQTC) with type I and type II reaction oxygen species (ROS) generation capabilities are synthesized. Notably, TQTPy shows mitochondria targeted capacity, the best ROS production efficiency, long-term tumor retention capacity, and more importantly, the three-in-one fluorescence imaging guided therapy against both tumor and microbial infections. Both in vitro and in vivo results validate that TQTPy performs well in practical biomedical application in terms of NIR-fluorescence imaging-guided photodynamic cancer diagnosis and treatment. Moreover, the amphiphilic and positively charged TQTPy is able to specific and ultrafast discrimination and elimination of Gram-positive (G+) Staphylococcus aureus from Gram-negative (G-) Escherichia coli and normal cells. This investigation provides an instructive way for the construction of three-in-one treatment for image-guided photodynamic cancer therapy and bacteria elimination.

Win-win integration: A mitochondria targeted AIE photosensitizer for hypochlorite detection and type I & type II photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO-) is a type of inflammatory cytokine. The abnormal increase of ClO- in tumor cells is related to tumor pathogenesis and may be a "friend" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. RESULTS: An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO- responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO- with fluorescence "turn on" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO- was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO- response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. SIGNIFICANCE AND NOVELTY: A win-win integration strategy was proposed to design a tumor intracellular ClO- responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.

A multifunctional fluorescent probe for sequential detection of hydrogen sulfide and pH in foodstuffs, living cells and mice.

BACKGROUND: Cancer as a leading cause of premature death worldwide has become a major threat to human health due to the high incidence and mortality. Monitoring tumor markers are reliable and significantly important for early detection of cancers. In complex biological systems, it is of great urgency but still remains challenging to conceive a fluorescent probe with multiple tumor markers detection property. Hydrogen sulfide (H2S) and pH are two target biomarkers for diagnosis of early cancer. The preparation of a novel probe with H2S and pH dual detection functions is highly anticipated. RESULTS: Herein, a novel sequential detection probe HTPQ-HS for H2S and pH has been developed. In this system, HPQ (2-(2 -hydroxyphenyl)-4(3H)-quinazolinone) structure combined with triphenylamine is applied as the fluorophore, and 2, 4-dinitrophenylsulfonyl group is used as the recognition group. In the presence of H2S, HTPQ-HS is transformed into product HTPQ-OH which shows fluorescence enhancement (29-fold) at 525 nm in less than 4 min and further displays repeatable acid-base responsive ability. HTPQ-HS is able to sequentially response to H2S and pH in living cells and does not react directly with pH. Owing to the low cytotoxicity, HTPQ-HS is able to detect exogenous and endogenous H2S in colon cancer cells and mice, monitor H2S in inflammation model and in foodstuffs. As the environment changes from acidic to alkaline, the fluorescence intensity ratio (I470/I530) of product HTPQ-OH changes remarkably, illustrating the ratiometric fluorescent responsiveness to pH. SIGNIFICANCE AND NOVELTY: A multifunctional fluorescent probe HTPQ-HS for sequential detection of H2S and pH is synthesized. Probe HTPQ-OH realizes the monitoring of dynamic changes in intracellular pH and displays prospective application in security printing. We expect that our work could offer an important guidance on the development of multifunctional fluorescent probes for visualizing H2S and pH in biology and environment.

A lysosome-targeted fluorescent probe based on a BODIPY structure for Cys/Hcy detection.

Cysteine (Cys) and homocysteine (Hcy) are important biothiols in living organisms. They play important roles in a variety of physiological and pathological processes. Therefore, it is very important to design an optical probe for the selective detection of Cys/Hcy. Herein, we report the design and synthesis of a fluorescent probe NBD-B-T based on a boron-dipyrromethene (BODIPY) structure, which showed an excellent lysosome targeting ability and an outstanding Cys/Hcy detection capacity. For NBD-B-T, the sensing group 7-nitro-2,1,3-benzoxadiazole (NBD) and the lysosomal targeting group morpholine were introduced. The results show that the NBD-B-T probe can detect Cys/Hcy with fluorescence emission turn-on performance. The low detection limits of this probe are about 76.0 nM for Hcy and 97.6 nM for Cys, respectively. The NBD-B-T probe has a low detection limit, high stability, and excellent selectivity and sensitivity. More importantly, the NBD-B-T can target lysosome, and simultaneously detect the Cys/Hcy in living cells.

Oxidative Aminoarylselenation of Maleimides via Copper-Catalyzed Four-Component Cross-Coupling.

The first example of copper-catalyzed four-component coupling reaction of aryl iodides, Se powder, secondary amines, and maleimides is developed. This reaction provides an efficient and concise route to access aminoarylselenated maleimides via double C-Se bonds and C-N bond formation. The appealing features of this transformation are the use of Se powder as a selenating reagent, a green catalytic system, a wide range of substrate scope, and late-stage selenation of bioactive compounds.

2,3-Dipentyldithieno[3,2-f:2',3'-h]quinoxaline-Based Organic Dyes for Efficient Dye-Sensitized Solar Cells: Effect of π-Bridges and Electron Donors on Solar Cell Performance.

Five novel metal-free organic dyes DQ1-5 containing a dipentyldithieno[3,2-f:2',3'-h]quinoxaline (DPQ) unit were synthesized and applied in dye-sensitized solar cells (DSSCs), where DPQ was employed as a π-spacer for the first time. Their photophysical, electrochemical, and theoretical calculations and photovoltaic properties were systematically investigated. All the five dyes show broad photoresponse. Especially the absorption edges of DQ3-5 extend to 800 nm on the TiO2 films. The inserted electron-rich unit 3,4-ethylenedioxythiophene or electron-withdrawing group benzothiadiazole (BTD) in DPQ-based dyes can greatly influence the optoelectronic properties of the dyes. In addition, the different electron donors also significantly affect the performance of the DSSCs. Under standard global AM 1.5 solar light conditions, the DQ5 sensitized solar cell obtained a power conversion efficiency of 7.12%. The result indicates that the rigid DPQ-based organic dye is a promising candidate for efficient DSSCs.