SpyGlass-Guided Photodynamic Therapy for Unresectable Cholangiocarcinoma: A Case Report and Review of the Literature.

Endoscopic retrograde cholangiopancreatography (ERCP) and biliary stent placement are standard palliative care procedures for patients with unresectable cholangiocarcinoma. However, the bile duct mucosa cannot be observed directly during the placement of a light diffuser in photodynamic therapy (PDT) and biopsy. SpyGlass can solve the above two problems. In this paper, we report the case of a patient who presented with obstructive jaundice and underwent endobiliary stenting placement several times. However, cholangiocarcinoma hyperplasia still led to stent blockage. We applied SpyGlass to guide the accurate placement of a light diffuser and evaluated the tumor necrosis after PDT. Results revealed the good application effect of this device.

Ligand and adjuvant dual-assisted synthesis of highly luminescent and stable Cs4PbBr6 nanoparticles used in LEDs.

We developed a new ligand and adjuvant dual-assisted room temperature colloidal method for the synthesis of highly luminescent and stable Cs4PbBr6 nanoparticles, in which acetone, oleamine (OM) and oleic acid (OA) were used as precursors, while water and dimethyl sulfoxide (DMSO) were used as adjuvants. In this process, we explored the influencing factors of process parameters (such as the amount of water, the standing time of precursors, and the molar ratio of raw materials), and found that Cs4PbBr6 synthesized by water + DMSO can not only change the morphology and promote crystallization but also improve the lattice strain, reduce the lattice defects and optimize the passivation effect, so as to improve the luminescence properties. Simultaneously, we also found that the pc-LED made of Cs4PbBr6 can still emit bright green light after 4344 h of operation, showing excellent stability and making it promising for solid-state lighting application. This method also provides an important reference value for solving the hydrolysis property of perovskites.

Improvement in optical properties of Cs4PbBr6 nanocrystals using aprotic polar purification solvent.

We demonstrate the influence mechanism on the optical property of Cs4PbBr6 during purification of solution with different protonated levels and polarities. During the purification process, organic groups originating from oleic acid (OA) and PbBr impurity on the surface of Cs4PbBr6 nanocrystals can be removed using high polarity aprotic and protonic solvents, and the number of Br vacancies (V Br) can be reduced. The protonic polar solvent can not only etch the organic groups on the surface of nanocrystals, causing surface reconstruction and particle growth of nanocrystals, but also enter into the lattice of Cs4PbBr6 and react with the embedded CsPbBr3. However, aprotic polar solvent decreases the particle size of Cs4PbBr6 nanocrystals with the increase in the solvent polarity. The optical properties of Cs4PbBr6 can be effectively improved using aprotic polar solvents as a purification solvent, which is very significant to improve the luminescence efficiency of perovskites.

Copper-Cysteamine Nanoparticles as a Heterogeneous Fenton-Like Catalyst for Highly Selective Cancer Treatment.

Herein, for the first time, we report copper-cysteamine (Cu-Cy) nanoparticles having Cu1+ instead of Cu2+ as an efficient heterogeneous Fenton-like catalyst for highly selective cancer treatment. Initial measurements of Cu-Cy's hydroxyl radical generation ability show that it behaves as a Fenton-like reagent in the presence of H2O2 (100 µM) at pH 7.4, and that its Fenton-like activity is dramatically enhanced under acidic conditions (pH 6.5 and 5.5). Notably, Cu-Cy exhibits high stability and minimal copper release during the Fenton-like reaction, demonstrating its potency as a heterogeneous Fenton-like catalyst with a low cytotoxic effect. Through extensive in vitro studies, Cu-Cy NPs are found to generate a significantly higher level of ROS, thereby causing significantly more destruction to cancerous cells than to normal cells without the need for exogenous additives, such as H2O2. To the best of our knowledge, the average IC-50 value of Cu-Cy to cancer cells (11 µg/mL) is the lowest among reported heterogeneous Fenton-like nanocatalyst so far. Additionally, compared to cancer cells, Cu-Cy NPs display substantially higher IC-50 value toward normal cells (50 µg/mL), suggesting high selectivity. Overall, Cu-Cy NPs can participate in heterogeneous Fenton-like activity with elevated H2O2 under acidic conditions to produce significantly higher levels of hydroxyl radicals in cancer cells when compared to normal cells, resulting in selective cytotoxicity to cancer cells.

A facile method for the synthesis of copper-cysteamine nanoparticles and study of ROS production for cancer treatment.

Copper-cysteamine (Cu-Cy) is a novel sensitizer that can be excited by ultraviolet (UV) light, microwave (MW), ultrasound, and X-rays to generate highly toxic reactive oxygen species (ROS) for cancer cell destruction. The purpose of this study is to present a facile method for the synthesis of Cu-Cy nanoparticles. Interestingly, we were able to decrease both the stirring and heating time by about 24 and 6 times, respectively, thus making Cu-Cy nanoparticles more economical than what was reported before. 1,4-Diazabicylo[2.2.2]octane (DABCO), a well-known singlet oxygen quencher, showed that the majority of ROS produced by Cu-Cy nanoparticles upon UV and MW exposure were singlet oxygen. Moreover, ROS generated by Cu-Cy nanoparticles upon UV and MW exposure were confirmed by a known ROS tracking agent, dihydrorhodamine 123, further serving as an additional piece of evidence that Cu-Cy is a promising ROS generating agent to destroy cancer cells as well as bacteria or viruses by a radical therapeutic approach. Additionally, for the first time, the hydroxyl radical (˙OH) produced by Cu-Cy nanoparticles upon MW activation was proved by a photoluminescence (PL) technique using coumarin as a probe molecule. Remarkably, newly synthesized nanoparticles were found to be much more effective for producing ROS and killing cancer cells, suggesting that the new method may have increased the reactivity of the Cu-Cy nanoparticles due to an overall size reduction. Overall, the new method not only reduced the synthesis time but also enhanced the effectiveness of Cu-Cy nanoparticles for photodynamic therapy.

3D modeling of cancer stem cell niche.

Cancer stem cells reside in a distinct microenvironment called niche. The reciprocal interactions between cancer stem cells and niche contribute to the maintenance and enrichment of cancer stem cells. In order to simulate the interactions between cancer stem cells and niche, three-dimensional models have been developed. These in vitro culture systems recapitulate the spatial dimension, cellular heterogeneity, and the molecular networks of the tumor microenvironment and show great promise in elucidating the pathophysiology of cancer stem cells and designing more clinically relavant treatment modalites.

Facile synthesis and excellent microwave absorption properties of FeCo-C core-shell nanoparticles.

FeCo-C core-shell nanoparticles (NPs) with diameters of 10-50 nm have been fabricated on a large scale by one-step metal-organic chemical vapor deposition using the mixture of cobalt acetylacetonate and iron acetylacetonate as the precursor. The Fe/Co molar ratio of the alloy nanocores and graphitization degree of C shells, and thus the magnetic and electric properties of the core-shell NPs, can be tuned by the deposition temperature ranging from 700 °C to 900 °C. Comparative tests reveal that a relatively high Fe/Co molar ratio and low graphitization degree benefit the microwave absorption (MA) performance of the core-shell NPs. The composite with 20 wt% core-shell NP obtained at 800 °C and 80 wt% paraffin exhibits an optimal reflection loss [Formula: see text] of -60.4 dB at 7.5 GHz with a thickness of 3.3 mm, and an effective absorption bandwidth (frequency range for RL ≤10 dB) of 9.2 GHz (8.8-18.0 GHz) under an absorber thickness of 2.5 mm. Our study provides a facile route for the fabrication of alloy-C core-shell nanostructures with high MA performance.

[Role of PpIX-based photodynamic therapy in promoting the damage and apoptosis of colorectal cancer cell and its mechanisms].

OBJECTIVE: To explore the effects of protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) on induction of apoptosis and death in colon cancer cell and the underlying mechanisms.
 Methods: The cell killing effect of PDT on HCT116 cell was determined by cell counting kit (CCK). The cells were divided into a control group, a single light group, a single PpIX group, and a PDT group. Hoechst 33342 and flow cytometry was used to assess the cell apoptosis. Western blot was employed to analyze the expressions of bcl-2, bax, and caspase-3. Reactive oxygen species (ROS) was detected by flow cytometry.
 Results: The viability of HCT116 cell was decreased gradually with the increase of irradiation dose (P<0.05). Compared to the other 3 groups, ROS production, the number of apoptotic cells and the protein expressions of bax and caspase-3 in PDT group increased, while bcl-2 expression was decreased (P<0.05).
 Conclusion: PpIX-mediated PDT can enhance the apoptosis in HCT116 cell, which may be related to mitochondrial apoptosis pathway.

Investigation of Copper Cysteamine Nanoparticles as a New Type of Radiosensitiers for Colorectal Carcinoma Treatment.

Copper Cysteamine (Cu-Cy) is a new photosensitizer and a novel radiosensitizer that can be activated by light, X-ray and microwave to produce singlet oxygen for cancer treatment. However, the killing mechanism of Cu-Cy nanoparticles on cancer cells is not clear yet and Cu-Cy nanoparticles as novel radiosensitizers have never been tested on colorectal cancers. Here, for the first time, we investigate the treatment efficiency of Cu-Cy nanoparticles on SW620 colorectal cells and elucidate the underlying mechanisms of the effects. The results show that X-ray activated Cu-Cy nanoparticles may kill SW620 cancerscells is in a dose-dependent manner. The JC-1 staining shows the mitochondrial membrane potential is decreased after the treatment. The observations confirm that Cu-Cy nanoparticles may improve X-ray radiotherapy on cancer treatment and X-ray activated Cu-Cy nanoparticles can be efficiently destroy colorectal cancer cells by inducing apoptosis as well as autophagy. As a new type of radiosensitizers and photosensitizers, Cu-Cy nanoparticles have a good potential for colorectal cancer treatment and the discovery of autophagy induced by X-ray irradiated Cu-Cy nanoparticles sheds a good insight to the mechanism of Cu-Cy for cancer treatment as a new radiosensitizers.

Autophagy inhibition enhances photocytotoxicity of Photosan-II in human colorectal cancer cells.

Photodynamic therapy (PDT) has emerged as an attractive therapeutic treatment for colorectal cancer because of its accessibility through endoscopy and its ability to selectively target tumors without destroying the anatomical integrity of the colon. We therefore investigated the therapeutic relevance of the interplay between autophagy and apoptosis in Photosan-II (PS-II)-mediated photodynamic therapy (PS-PDT) in in vitro and in vivo models for human colorectal cancer. We observed that PS-PDT-induced dose-dependently triggered apoptosis and autophagy in both SW620 and HCT116 cells. PS-PDT-treated SW620 cells exhibited nuclear condensation and increased levels of cleaved caspase-3, PARP and Bax, which is reminiscent of apoptosis. PS-PDT also induced autophagic vacuoles, double membrane autophagosome structures and the autophagy-related proteins P62, Bcl-2, ATG7 and LC3-II. In addition, the AKT-mTOR pathway was downregulated, while AMPK was upregulated in PS-PDT-treated cells. Inhibiting autophagy using chloroquine or by downregulating ATG7 using shRNA further upregulated apoptosis, suggesting autophagy was probably was protective to PS-PDT-treated tumor cells. In vivo relevance was demonstrated when a combination of chloroquine and PS-PDT significantly reduced the tumor size in a xenograft mice model. Our findings demonstrate that combination therapy using PS-PDT and autophagy inhibitors may be an effective approach to treating colorectal cancer patients.

Nanoscale Photodynamic Agents for Colorectal Cancer Treatment: A Review.

Colorectal cancer is the most common form of gastroenteric cancer worldwide. Photodynamic therapy is emerging as an attractive method to treat cancers. Candidate targets of photodynamic therapy include epidermal growth factor receptors, cholesterol and low-density lipoprotein, estrogen receptors, the nucleus and DNA, folic acid receptors, cholecystokinin A receptors, lectin saccharide receptors, and tumor-specific antibodies. Specifically, in colorectal tumors, anti-DR5 antibody and cancer-specific antibody moieties are involved. Cancer cells incorporate greater quantities of sugars, and glycoconjugated photosensitizer has remarkable internalization and cytotoxicity in colon/colorectal cancer cells. Simultaneously, to circumvent the bio-distribution limitation, other molecules, including lectins, Hyaluronic acid, and peptides, have also been considered for colorectal cancer. Other novel strategies indirectly targeting colorectal cancer include pH-responsive PS, enzymatically activated photosensitization, and cancer-suppressing immune cells, mainly macrophages. Recently, nanoparticles have gained attention as a versatile platform for multi-functional photodynamic therapy. In this review, we summarize the targeting strategies investigated and highlight the potential of nanoparticles for target photodynamic therapy in colorectal cancer.

Active Targeting of Nano-Photosensitizer Delivery Systems for Photodynamic Therapy of Cancer Stem Cells.

Cancer stem cells are believed to be the basis for tumor initiation, development, metastasis and recurrence; are resistant to most traditional therapies (e.g., chemotherapy and radiotherapy); and have the ability to self-renew, proliferate and differentiate. Photodynamic therapy may be a promising novel treatment for drug-resistant cancer stem cells because of the selectivity of the photosensitizer. One of the most important issues to overcome in photodynamic therapy is the photosensitizer-targeted delivery to tumor cells, especially cancer stem cells. Nano-photosensitizers comprising molecular photosensitizers and water-dispersible nanocarriers with or without moieties possessing the ability for specific binding to cancer cells or cancer stem cells are a promising strategy for active targeted photosensitizer delivery and photodynamic therapy-targeted therapy of tumors. In this review, we highlight current and future prospects for potential strategies based on nanoscience and nanotechnology for nano-photosensitizer-targeted delivery in the photodynamic therapy treatment of cancer cells, especially cancer stem cells.

Fracture strain of SiC nanowires and direct evidence of electron-beam induced amorphisation in the strained nanowires.

SiC nanowires with diameters ranging from 29 to 270 nm exhibit an average strain of 5.5% with a maximum of up to 7.0%. The brittle fracture of the nano-wires being measured was confirmed by transmission electron microscopy (TEM) analysis. This study demonstrates that amorphisation occurs in the stained SiC nanowires during normal TEM examination, which could be induced by electron irradiation.

In vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer.

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II (p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.

Cytotoxicity of hollow silica nanoparticles loaded with photosensitizes on huh-7 cells.

To observe the cytotoxic effect of the photodynamic therapy mediated by the traditional photosensitizer polyhematoporphyrin (C(34)H(38)N(4)NaO(5), Photosan-II Photosan-II was loaded into HSNP by one-step wet chemical, PS) and hollow silica nanoparticles (HSNP) loaded PS on Huh-7 cells and compare the cytotoxic effects. -based synthetic route. The cellular viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry. The suitable drug concentrations of free PS and HSNP loaded PS on Huh-7 cells were 20mg/L and 5mg/L respectively, and the suitable incubation time were 4 h and 2 h respectively. Under the same drug concentration, the survival rates of free PS and HSNP loaded PS were 62.46%±1.93% and 6.54%±1.24% <. Under the same drug concentration and incubation time, the total rates of apoptosis necrosis caused by free PS and HSNP loaded PS mediated PDT were respectively 22.00% ± 2.24% and 87.23% ± 2.1% <. PS-loaded HSNP mediated PDT can inhibit proliferation of cancer cells and induce apoptosis more quickly and effectively. As the loading system of PS, HSNP can make the photosensitizer have stronger solubility and drug concentration efficiency, which can significantly improve the therapeutic effect of PDT.

Luminescence behavior of Li2 Sr1-3x/2 Eux SiO4 red phosphors for LED applications.

Red-emitting Li(2)Sr(1-3x/2)Eux SiO4 0 ≤ x ≤ 0.5) phosphors were synthesized at 900 °C in air by a solid-state reaction. The synthesized phosphors were characterized by X-ray powder diffraction, photoluminescence (PL) excitation (PLE) and PL spectra. The results from the PLE spectra suggest that the strong 394 nm excitation peak associated with the (5) L6 state of Eu(3+) ions is of significance for near ultraviolet pumped white light-emitting diodes and solid-state lighting. It is also noted that the position of the charge transfer state of Eu(3+) ions shifts towards the higher energy side (blue shift) by increasing the content of Eu(3+) ions. The predominant emissions of Eu(3+) ions under 394 nm excitation are observed at 580, 593, 614, 656 and 708 nm, which are attributed to the (5) D0 → (7)FJ (J = 0, 1, 2, 3 and 4), respectively. The PL results reveal that the optimal content of the red-emitting Li2 Sr(1-3x/2)Eux SiO4 phosphors is x = 0.475. Simulation of the white light excited by 394 nm near ultraviolet light has also been carried out for its potential white light-emitting diode applications.

Photosan-II loaded hollow silica nanoparticles: preparation and its effect in killing for QBC939 cells.

BACKGROUND: Nanoparticles have been explored recently as an efficient means to deliver photosensitizers for photodynamic therapy. However, it is largely unknown if polyhematoporphyrin (C34H38N4NaO5, Photosan-II, PS) or other photosensitizers can be efficiently delivered by hollow silica nanoparticles (HSNP). METHODS: Polyhematoporphyrin (C34H38N4NaO5, Photosan-II, PS) was loaded into hollow silica nanoparticles (HSNP) by one-step wet chemical-based synthetic route. Dynamic light scattering (DLS) and polydispersive index (PDI) were used for measurement of the particles size and size distribution. Transmission electron microscope and scanning electron microscopy were used for the microstructure, morphological and chemical composition analysis. Fourier transform infrared spectrometry spectra and fluorescence emission spectrum were obtained. The photobiological activity of the PS-loaded HSNP was evaluated on human cholangiocarcinoma QBC939 cells. The cellular viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry. RESULTS: DLS measurements showed that the size of the particles is in the range of 25-90 nm. PDI of the PS-loaded HSNP is 0.121 ± 0.01, indicating that samples have excellent quality with narrow size distribution to monomodal systems. In MTT assay, PS-loaded HSNP and free PS of the same concentration killed about 95.3% ± 2.0% and 55.7% ± 1.9% of QBC939 cells, respectively. The flow cytometry demonstrated that the laser induced cell death with PS-loaded HSNP was much more severe than that of free PS (P<0.05). CONCLUSIONS: Photosan-II-loaded hollow silica nanoparticles not only can quickly deliver Photosan-II into cells but also can reach a more high concentration than free Photosan-II. HSNP is a desirable vehicle and the release system that shows promises for photodynamic therapy use, which not only improve the aqueous solubility, stability and transport efficiency of PS, but also increase its photodynamic efficacy compared to free PS.

Sol-hydrothermal synthesis and optical properties of Eu3+, Tb(3+)-codoped one-dimensional strontium germanate full color nano-phosphors.

Novel near-UV and blue excited Eu(3+), Tb(3+)-codoped one dimensional strontium germanate full-color nano-phosphors have been successfully synthesized by a simple sol-hydrothermal method. The morphologies, internal structures, chemical constitution and optical properties of the resulting samples were characterized using FE-SEM, TEM, HRTEM, EDS, XRD, FTIR, XPS, PL and PLE spectroscopy and luminescence decay curves. The results suggested that the obtained Eu(3+), Tb(3+)-codoped strontium germanate nanowires are single crystal nanowires with a diameter ranging from 10 to 80 nm, average diameter of around 30 nm and the length ranging from tens to hundreds micrometers. The results of PL and PLE spectra indicated that the Eu(3+), Tb(3+)-codoped single crystal strontium germanate nanowires showed an intensive blue, blue-green, green, orange and red or green, orange and red light emission under excitation at 350-380 nm and 485 nm, respectively, which may attributed to the coexistent Eu(3+), Eu(2+) and Tb(3+) ions, and the defects located in the strontium germanate nanowires. A possible mechanism of energy transfer among the host, Eu(3+) and Tb(3+) ions was proposed. White-emission can be realized in a single-phase strontium germanate nanowire host by codoping with Tb(3+) and Eu(3+) ions. The Eu(3+), Tb(3+)-codoped one-dimensional strontium germanate full-color nano-phosphors have superior stability under electron bombardment. Because of their strong PL intensity, good CIE chromaticity and stability, the novel 1D strontium germanate full-color nano-phosphors have potential applications in W-LEDs.

Synthesis and luminescent properties of novel BaGd2O4:Eu3+ scintillating phosphor.

BaGd2-x O4:xEu(3+) and Ba1-y Gd1.79-2y Eu0.21 Na3y O4 phosphors were synthesized at 1300°C in air by conventional solid-state reaction method. Phosphors were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence excitation (PLE) spectra, photoluminescence (PL) spectra and thermoluminescence (TL) spectra. Optimal PL intensity for BaGd2-x O4 :xEu(3+) and Ba1-y Gd1.79-2y Eu0.21 Na3y O4 phosphors at 276 nm excitation were found to be x = 0.24 and y = 0.125, respectively. The PL intensity of Eu(3+) emission could only be enhanced by 1.3 times with incorporation of Na(+) into the BaGd2 O4 host. Enhanced luminescence was attributed to the flux effect of Na(+) ions. However, when BaGd2 O4:Eu(3+) phosphors were codoped with Na(+) ions, the induced defects confirmed by TL spectra impaired the emission intensity of Eu(3+) ions.

Synthesis and optical property of large-scale centimetres-long silicon carbide nanowires by catalyst-free CVD route under superatmospheric pressure conditions.

Large-scale centimetres-long single-crystal ß-SiC nanowires have been prepared using CH(4) as the carbon source and SiO or the mixture of Si and SiO(2) as the silicon source by a simple catalyst-free CVD route under superatmospheric pressure conditions. The nanowries grown on ceramic boat or corundum substrates, with lengths of several centimetres and the average diameters of around 40 nm, were composed of single-crystal ß-SiC core along the [111] direction and amorphous SiO(2) shell of about 1-30 nm thick depending on the growth position along the flowing direction of the carrier gas. The total gas pressure is an important factor for the synthesis of the large-scale centimetres-long ß-SiC nanowires, which can easily adjust the pressure of the vapors to supersaturation condition. The growth of the nanowires was governed by the Vapor-Solid mechanism. The ß-SiC nanowires showed an intense blue light emission at room temperature.