Hypericin-mediated photodynamic therapy inhibits metastasis and EMT of colorectal cancer cells by regulating RhoA-ROCK1 signaling pathway.

Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.

The isosbestic point in the Raman spectra of the hydration shell.

Isosbestic point is often observed in a series of spectra, but their interpretation is still controversial, such as whether the continuum model can produce an isosbestic point. In order to answer this question, the Raman spectra of hydration shell with continuous distribution structure in different ionic aqueous solutions were separated by Raman ratio spectra, and an isosbestic point was successfully observed. Our experimental results show that the continuum model can indeed produce the isosbestic point. In order to deepen the understanding of the isosbestic point, we calculate the first moment of the Raman spectra and conduct molecular dynamics (MD) simulations. Both experimental and theoretical findings indicate that elevated temperatures lead to increased disorder among water molecules within the hydration shell.

Hypericin-mediated photodynamic therapy inhibits growth of colorectal cancer cells via inducing S phase cell cycle arrest and apoptosis.

Colorectal cancer (CRC) is one type of cancer with high morbidity and mortality worldwide. Photodynamic therapy (PDT), a promising new therapeutic approach for cancer, induces tumor damage through photosensitizer-mediated oxidative cytotoxicity. Hypericin is a powerful photosensitizer with pronounced tumor-localizing properties. In this study, we investigated the phototoxic effects of hypericin-mediated PDT (HYP-PDT) in HCT116 and SW620 cells. We validated that HYP-PDT inhibited cell proliferation, triggered intracellular reactive oxygen species generation, induced S phase cell cycle arrest and apoptosis of HCT116 and SW620 cells. Mechanistically, the results of western blot showed that HYP-PDT downregulated CDK2 expression through decreasing the CDC25A protein, which resulted in the decrease of CDK2/Cyclin A complex. Additionally, HYP-PDT induced DNA damage as evidenced by ATM activation and upregulation of p-H2AX. Further investigation showed that HYP-PDT significantly increased Bax expression and decreased Bcl-2 expression, and then, upregulated the expression of cleaved caspase-9, cleaved caspase-3 and cleaved PARP, thereby inducing apoptosis in HCT116 and SW620 cells. In conclusion, our results indicated that the CDC25A/CDK2/Cyclin A pathway and the mitochondrial apoptosis pathway were involved in HYP-PDT induced S phase cell cycle arrest and apoptosis in colorectal cancer cells, which shows HYP could be a probable candidate used for treating colorectal cancer.

Infrared and visible image perceptive fusion through multi-level Gaussian curvature filtering image decomposition.

The aim of infrared and visible image fusion is to obtain an integrated image that contains obvious object information and high spatial resolution background information. The integrated image is more conductive for a human or a machine to understand and mine the information contained in the image. To attain this purpose, a fusion algorithm based on multi-level Gaussian curvature filtering (MLGCF) image decomposition is proposed. First, a MLGCF is presented and employed to decompose the input source images into three different layers: small-scale, large-scale, and base layers. Then, three fusion strategies-max-value, integrated, and energy-based-are applied to combine the three types of layers, which are based on the different properties of the three types of layers. Finally, the fusion image is reconstructed by summing the three types of fused layers. Six groups of experiments demonstrate that the proposed algorithm performs effectively in most cases by subjective and objective evaluations and even exceeds many high-level fusion algorithms.

Polyelectrolyte-Mediated Nontoxic AgGa xIn1- xS2 QDs/Low-Density Lipoprotein Nanoprobe for Selective 3D Fluorescence Imaging of Cancer Stem Cells.

Cancer stem cells, which are a population of cancer cells sharing common properties with normal stem cells, have strong self-renewal ability and multi-lineage differentiation potential to trigger tumor proliferation, metastases, and recurrence. From this, targeted therapy for cancer stem cells may be one of the most promising strategies for comprehensive treatment of tumors in the future. We design a facile approach to establish the colon cancer stem cells-selective fluorescent probe based on the low-density lipoprotein (LDL) and the novel AgGa xIn(1- x)S2 quantum dots (AGIS QDs). The AGIS QDs with a high crystallinity are obtained for the first time via cation-exchange protocol of Ga3+ to In3+ starting from parent AgInS2 QDs. Photoluminescence peak of AGIS QDs can be turned from 502 to 719 nm by regulating the reaction conditions, with the highest quantum yield up to 37%. Subsequently, AGIS QDs-conjugated LDL nanocomposites (NCs) are fabricated, in which a cationic polyelectrolyte was used as a coupling reagent to guarantee the electrostatic self-assembly. The structural integrity and physicochemical properties of the LDL-QDs NCs are found to be maintained in vitro, and the NCs exhibit remarkable biocompatibility. The LDL-QDs can be selectively delivered into cancer stem cells that overexpress LDL receptor, and three-dimensional imaging of cancer stem cells is realized. The results of this study not only demonstrate the versatility of nature-derived lipoprotein nanoparticles, but also confirm the feasibility of electrostatic conjugation using cationic polyelectrolyte, allowing reseachers to design nanoarchitectures for targeted diagnosis and treatment of cancer.

Well-Hidden Grain Boundary in the Monolayer MoS2 Formed by a Two-Dimensional Core-Shell Growth Mode.

Guided by the hexagonal lattice symmetry, triangles and hexagons are the most basic morphological units for two-dimensional (2D) transition metal dichalcogenides (TMDs) synthesized by chemical vapor deposition (CVD). Also, it is widely acknowledged that these units start from the single nucleation site and then grow epitaxially. Accordingly, the triangular monolayer (ML) samples are generally considered as single crystals. Here, we report a 2D core-shell growth mode in the CVD process for ML-MoS2, which leads to one kind of "pseudo" single-crystal triangles containing triangular outline grain boundaries (TO-GBs). It is difficult to be optically distinguished from the "true" single-crystal triangles. The weakening of Raman peaks and the remarkable enhancement of photoluminescence (PL) are found at the built-in TO-GBs, which could be useful for high-performance optoelectronics. In addition, the electrical measurements indicate that the TO-GBs are conductive. Furthermore, TO-GBs and the common grain boundaries (CO-GBs) can coexist in a single flake, whereas their optical visibility and optical modifications (Raman and PL) are quite different. This work is helpful in further understanding the growth mechanism of 2D TMD materials and may also play a significant role in related nanodevices.

Bandgap and Structure Engineering via Cation Exchange: From Binary Ag2S to Ternary AgInS2, Quaternary AgZnInS alloy and AgZnInS/ZnS Core/Shell Fluorescent Nanocrystals for Bioimaging.

Attention on semiconductor nanocrystals have been largely focused because of their unique optical and electrical properties, which can be applied as light absorber and luminophore. However, the band gap and structure engineering of nanomaterials is not so easy because of their finite size. Here we demonstrate an approach for preparing ternary AgInS2 (AIS), quaternary AgZnInS (AZIS), AgInS2/ZnS and AgZnInS/ZnS nanocompounds based on cation exchange. First, pristine Ag2S quantum dots (QDs) with different sizes were synthesized in one-pot, followed by the partial cation exchange between In(3+) and Ag(+). Changing the initial ratio of In(3+) to Ag(+), reaction time and temperature can control the components of the obtained AIS QDs. Under the optimized conditions, AIS QDs were obtained for the first time with a cation disordered cubic phase and high photoluminescence (PL) quantum yield (QY) up to 32% in aqueous solution, demonstrating the great potential of cation exchange in the synthesis for nanocrystals with excellent optical properties. Sequentially, Zn(2+) ions were incorporated in situ through a second exchange of Zn(2+) to Ag(+)/In(3+), leading to distinct results under different reaction temperature. Addition of Zn(2+) precursor at room temperature produced AIS/ZnS core/shell NCs with successively enhancement of QY, while subsequent heating could obtain AZIS homogeneous alloy QDs with a successively blue-shift of PL emission. This allow us to tune the PL emission of the products from 483 to 675 nm and fabricate the chemically stable QDs core/ZnS shell structure. Based on the above results, a mechanism about the cation exchange for the ternary nanocrystals of different structures was proposed that the balance between cation exchange and diffusion is the key factor of controlling the band gap and structure of the final products. Furthermore, photostability and in vitro experiment demonstrated quite low cytotoxicity and remarkably promising applications in the field of clinical diagnosis.

Bio-compatibility and cytotoxicity studies of water-soluble CuInS2-ZnS-AFP fluorescence probe in liver cancer cells.

BACKGROUND: The oncogenesis of hepatocellular carcinoma (HCC) is not clear. The current methods of the pertinent studies are not precise and sensitive. The present study was to use liver cancer cell line to explore the bio-compatibility and cytotoxicity of ternary quantum dots (QDs) probe and to evaluate the possible application of QDs in HCC. METHODS: CuInS2-ZnS-AFP fluorescence probe was designed and synthesized to label the liver cancer cell HepG2. The cytotoxicity of CuInS2-ZnS-AFP probe was evaluated by MTT experiments and flow cytometry. RESULTS: The labeling experiments indicated that CuInS2-ZnS QDs conjugated with AFP antibody could enter HepG2 cells effectively and emit intensive yellow fluorescence by ultraviolet excitation without changing cellular morphology. Toxicity tests suggested that the cytotoxicity of CuInS2-ZnS-AFP probe was significantly lower than that of CdTe-ZnS-AFP probe (t test, F=0.8, T=-69.326, P<0.001). For CuInS2-ZnS-AFP probe, time-effect relationship was presented in intermediate concentration (>20%) groups (P<0.05) and dose-effect relationship was presented in almost all of the groups (P<0.05). CONCLUSION: CuInS2-ZnS-AFP QDs probe had better bio-compatibility and lower cytotoxicity compared with CdTe-ZnS-AFP probe, and could be used for imaging the living cells in vitro.

Tumor cell-targeted Zn3In2S6 and Ag-Zn-In-S quantum dots for color adjustable luminophores.

We present a hydrothermal approach for the preparation of biocompatible and high-quality Zn3In2S6 (ZIS) quantum dots (QDs) in the presence of glutathione (GSH) as a stabilizer at different reaction temperatures. The as-prepared QDs exhibited small particle diameters (from 3.3 to 7.5 nm) with a hexagonal structure and size-dependent optical properties. The combination of the pH value and the amount of GSH played a crucial role in the enhancement of PL intensity. After the incorporation of Ag via cation exchange, the obtained Ag-Zn-In-S (AZIS) QDs demonstrated both red-shifted photo-luminescence (PL) emission and higher quantum yield. Furthermore, based on the investigations of PL lifetimes and excitation intensity-dependent PL spectra, we concluded that PL emission of ZIS QDs originated from shallow donor-acceptor (D-A) pair recombination, and intrinsic trap state-related deep D-A pair transition dominated the main emission of AZIS QDs. Furthermore, the biocompatible AZIS QDs with high quantum yield were applied to targeted labeling and imaging in the cytoplasm of hepatocellular carcinoma cells, indicating their promising applications in single-cell monitoring.

Au-Ag@Au Hollow Nanostructure with Enhanced Chemical Stability and Improved Photothermal Transduction Efficiency for Cancer Treatment.

Despite the fact that Au-Ag hollow nanoparticles (HNPs) have gained much attention as ablation agents for photothermal therapy, the instability of the Ag element limits their applications. Herein, excess Au atoms were deposited on the surface of a Au-Ag HNP by improving the reduction power of l-ascorbic acid (AA) and thereby preventing the reaction between HAuCl4 and the Ag element in the Au-Ag alloy nanostructure. Significantly, the obtained Au-Ag@Au HNPs show excellent chemical stability in an oxidative environment, together with remarkable increase in extinction peak intensity and obvious narrowing in peak width. Moreover, finite-difference time-domain (FDTD) was used to simulate the optical properties and electric field distribution of HNPs. The calculated results show that the proportion of absorption cross section in total extinction cross section increases with the improvement of Au content in HNP. As predicted by the theoretical calculation results, Au-Ag@Au nanocages (NCs) exhibit a photothermal transduction efficiency (η) as high as 36.5% at 808 nm, which is higher than that of Au-Ag NCs (31.2%). Irradiated by 808 nm laser at power densities of 1 W/cm(2), MCF-7 breast cancer cells incubated with PEGylated Au-Ag@Au NCs were seriously destroyed. Combined together, Au-Ag@Au HNPs with enhanced chemical stability and improved photothermal transduction efficiency show superior competitiveness as photothermal agents.

CVD synthesis of Mo((1-x))W(x)S2 and MoS(2(1-x))Se(2x) alloy monolayers aimed at tuning the bandgap of molybdenum disulfide.

As a rising star in two-dimensional (2D) layered materials, transition metal dichalcogenides (TMDs) have attracted tremendous attention for their potential applications in nanoelectronics, optoelectronics and photonics. Driven by the high standards of practical devices, alloying theory has been proposed for modulating the electronic structure of TMDs materials as well as their physical and chemical properties. To date, however, very limited alloy materials can be synthesized by chemical vapor deposition (CVD) and a very limited band gap range can be achieved. Herein, for the first time, we report a one-step CVD strategy for the growth of ternary alloy Mo(1-x)WxS2 monolayers (ML) on SiO2/Si substrates with controllable composition. Both Mo(1-x)WxS2 and MoS2(1-x)Se2x alloy materials with high crystallinity were synthesized in this study. Therefore, the bandgap photoluminescence (PL) can be broaden from 1.97 eV (for ML-WS2) to 1.55 eV (for ML-MoSe2). Furthermore, density functional theory calculations were performed to reveal the important role of alloying in tailoring the electronic structure of 2D materials.

Facile synthesis of water-soluble Zn-doped AgIn5S8/ZnS core/shell fluorescent nanocrystals and their biological application.

Here we demonstrate a novel and facile strategy of highly luminescent water-soluble Zn-doped AgIn5S8 (ZAIS) nanocrystals and ZAIS/ZnS core/shell structures, which were based on hydrothermal reaction between the acetate salts of the corresponding metals and sulfide precursor in the presence of l-cysteine at 110 °C in a Teflon-lined autoclave. The photoluminescent (PL) emission wavelength can be conveniently tuned from 560 to 650 nm by tailoring the stoichiometric ratio of [Ag]/[Zn]. The as prepared nanocrystals were characterized systematically and exhibit long PL lifetimes more than 100 ns. The influence of experimental conditions, including concentration of l-cysteine and reaction temperature, was investigated. In addition, we performed a coating procedure with the ZnS shell outside the ZAIS core and showed excellent PL quantum yields up to 35%. The in vitro experiment exhibited quite low cytotoxicity and marvelous biocompatibility, revealing their promising prospect in bioscience. Furthermore, the obtained ZAIS/ZnS nanocompounds (NCs) were covalently conjugated to alpha-fetoprotein antibodies and targeted fluorescent imaging for hepatocellular carcinoma cells was realized.

Aqueous synthesis of color tunable Cu doped Zn-In-S/ZnS nanoparticles in the whole visible region for cellular imaging.

Cu doped Zn-In-S quantum dots (CZIS QDs) were synthesized by a hydrothermal method. The absorption and fluorescence peaks of CZIS QDs shifted monotonically to longer wavelengths with the increase of the Cu precursor and the decrease of Zn and In precursors. The dopant emission wavelength can be easily tuned in the whole visible region ranging from 465 nm to 700 nm by changing the molar ratio of Cu/Zn/In/S. On the basis of experimental results, it was testified that the emission of CZIS QDs was the trap state emission rather than the excitonic emission. The emission mechanisms of CZIS QDs were attributed to three kinds of approaches: (i) photogenerated holes efficiently move to trap states induced by Cu defects and recombine with the electrons in the energy level of sulfur vacancies; (ii) the holes in Cu trap states recombine with the electrons in the surface defect state; (iii) the electrons in the conduction band recombine with the holes in levels caused by Zn vacancies. After coating the ZnS shell around the CZIS core, the fluorescence quantum yield of CZIS QDs can reach 25-35%. CZIS/ZnS QDs conjugated with antibodies were successfully applied for labeling Hep-G2 liver cancer cells. The cytotoxicity studies revealed that the viabilities of the cells incubated with different concentrations of CZIS/ZnS QDs and at different times all remained at a high level of more than 90%. Hence, the CZIS/ZnS nanoparticle is a promising material as the fluorescent probe for biological applications.