Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9 +/- 1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96 +/- 1.88)% compared with (0.99 +/- 0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9 +/- 1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96 +/- 1.88)% compared with (0.99 +/- 0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy

Effects of Process Parameters on Microstructure and Mechanical Properties of Semi-Solid Al-7Si-0.5Mg Aluminum Alloy by Gas Induced Semi-Solid Process

Al-7Si-0.5Mg aluminum alloy semi-solid slurry with good spherical grains was prepared by gas induced semi-solid process (GISS) and the effects of both holding time and medium alloy addition on the microstructure of the semi-solid slurry were investigated. These two parameters have a great influence on the solid fraction, the size and the sphericity of the grains. With holding time increased from 85 s to 270 s, the solid phase fraction of the semi-solid slurry decreased from ~0.77 to ~0.67, the average grain size increased from ~95 μm to ~225 μm and the average shape factor decreased from ~0.80 to ~0.33. When medium alloy addition varied in the range of 0.5–2.0 wt%, a better slurry microstructure was obtained at about 1.5 wt%. Compared with the conventional liquid die-casting, the semi-solid die-casting improved the mechanical properties of tensile bars; yield strength, tensile strength and elongation of tensile bars reached ~240 MPa, ~307 MPa and ~8.8% after heat treatment, respectively. In conclusion, GISS process can prepare the semi-solid slurry with uniform and round microstructure, and the semi-solid die-casting can improve mechanical proper ties of Al-7Si-0.5Mg aluminum alloy

Role of miR-182 in response to oxidative stress in the cell fate of human fallopian tube epithelial cells

High grade serous ovarian carcinoma (HGSC) is a DNA instable tumor and its precursor is commonly found originating from the fimbriated end of the fallopian tube secretory epithelial (FTSE) cells. The local stresses via ovulation and related inflammation are risks for HGSC. In this study, we examined the cellular and molecular responses of FTSE cells to stress. We found that excess intracellular reactive oxygen species (ROS) in normal FTSE cells upregulated a subset of microRNA expression (defined as ROSmiRs). Most ROSmiRs' expression and function were influenced and regulated by p53, and together they drove the cells into stress-induced premature senescence (SIPS). However, ROS-induced miR-182 is regulated by β-catenin, not by p53. In normal FTSE cells, miR-182 overexpression triggers cellular senescence by p53-mediated upregulation of p21. Conversely, in cells with p53 mutations, miR-182 overexpression no longer enhances p21 but functions as an “Onco-miR”. p53 dysfunction is a prerequisite for miR-182-mediated tumorigenesis. In addition, we found that human follicular fluid could significantly induce intracellular ROS in normal FTSE cells. These findings suggest that ROS and p53 mutations may trigger a series of events, beginning with overexpressing miR-182 by ROS and β-catenin, impairing the DNA damage response, promoting DNA instability, bypassing senescence and eventually leading to DNA instable tumors in FTSE cells

Fabrication of Porous TiO2 Hollow Spheres and Their Application in Gas Sensing

In this work, porous TiO2 hollow spheres with an average diameter of 100 nm and shell thickness of 20 nm were synthesized by a facile hydrothermal method with NH4HCO3 as the structure-directing agent, and the formation mechanism for this porous hollow structure was proved to be the Ostwald ripening process by tracking the morphology of the products at different reaction stages. The product was characterized by SEM, TEM, XRD and BET analyses, and the results show that the as-synthesized products are anatase phase with a high surface area up to 132.5 m2/g. Gas-sensing investigation reveals that the product possesses sensitive response to methanal gas at 200°C due to its high surface area

Fabrication of Porous TiO₂ Hollow Spheres and Their Application in Gas Sensing

Abstract In this work, porous TiO2 hollow spheres with an average diameter of 100 nm and shell thickness of 20 nm were synthesized by a facile hydrothermal method with NH4HCO3 as the structure-directing agent, and the formation mechanism for this porous hollow structure was proved to be the Ostwald ripening process by tracking the morphology of the products at different reaction stages. The product was characterized by SEM, TEM, XRD and BET analyses, and the results show that the as-synthesized products are anatase phase with a high surface area up to 132.5 m2/g. Gas-sensing investigation reveals that the product possesses sensitive response to methanal gas at 200&#176;C due to its high surface area.</p

A Glucose Sensor Based on Glucose Oxidase Immobilized by Electrospinning Nanofibrous Polymer Membranes Modified with Carbon Nanotubes

A glucose biosensor based on glucose oxidase immobilized by electrospinning nanofibrous membranes has been developed. Nanofibrous membranes were electrospun from the solution of poly(acrylonitrile-co-acrylic acid) containing carbon nanotubes suspension and directly deposited on Pt electrodes for immobilizing glucose oxidase. The morphologies and structure of the nanofibrous membranes with or without carbon nanotubes were characterized by scanning electron microscopy. The fabrication parameters of nanofibers were optimized such as thickness of the nanofibrous membranes and mass ration of carbon nanotubes. The biosensor showed the relationship with a concentration range of 0.1–10 mM and response time was 60 s. The sensitivity of carbon nanotubes modified biosensors was two times larger than which of no carbon nanotubes modified ones. The pH effect, interference and lifetime of biosensors were discussed

A factory fracturing model of multi-well cluster in Sulige gas field, NW China

Sulige gas field is a typical low-permeability reservoir in China. According to desert landform features along with the regional hydrologic feature and the existing fracturing technology and operational conditions, a factory-like fracturing method suitable for Sulige gas field is established to improve techniques and production organization. This method includes five key parts: (1) centralized water supply mode (water source well supply+artificial lake storage); (2) highly efficient fracturing process (two mature multi-stage fracturing technologies, sliding sleeve fracturing for vertical wells and open-hole packer fracturing for horizontal wells); (3) pipeline operation mode with seven procedures, including well drift and flushing perforation etc; (4) high efficiency operation equipment; (5) recovery of fracturing flow-back fluid. This method shortens the preparation and operation period of fracturing treatment and also relieves the pressure on environment. Pilot tests were carried out in 11 well groups in total. Sixty-seven stages of fracturing in 14 wells were successfully completed within 42 days, representing a reduction of fracturing operation cycle of more than 50%, and an encouraging improvement in efficiency. Key words: Sulige gas field, factory fracturing, big well group, water supply, fracturing process, pipeline operation, fluid recovery, high efficiency, environment friendl

Effects of Process Parameters on Microstructure and Mechanical Properties of Semi-Solid Al-7Si-0.5Mg Aluminum Alloy by Gas Induced Semi-Solid Process

Al-7Si-0.5Mg aluminum alloy semi-solid slurry with good spherical grains was prepared by gas induced semi-solid process (GISS) and the effects of both holding time and medium alloy addition on the microstructure of the semi-solid slurry were investigated. These two parameters have a great influence on the solid fraction, the size and the sphericity of the grains. With holding time increased from 85 s to 270 s, the solid phase fraction of the semi-solid slurry decreased from ~0.77 to ~0.67, the average grain size increased from ~95 &mu;m to ~225 &mu;m and the average shape factor decreased from ~0.80 to ~0.33. When medium alloy addition varied in the range of 0.5&ndash;2.0 wt%, a better slurry microstructure was obtained at about 1.5 wt%. Compared with the conventional liquid die-casting, the semi-solid die-casting improved the mechanical properties of tensile bars; yield strength, tensile strength and elongation of tensile bars reached ~240 MPa, ~307 MPa and ~8.8% after heat treatment, respectively. In conclusion, GISS process can prepare the semi-solid slurry with uniform and round microstructure, and the semi-solid die-casting can improve mechanical properties of Al-7Si-0.5Mg aluminum alloy