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Ursolic acid (UA) has shown great potential in cancer therapy but their efficacy is seriously compromised by poor water-solubility and limited cellular uptake. In this paper, cationic nanomicelles self-assembled from Pluronic F127 with the cationic polymer of C18-polyethylenimine (C18-PEI) as a functional component are fabricated as delivery vehicles of Chinese herbal medicine active components of ursolic acid (UA) for colorectal cancer treatment. The inhibition effects of this drug loaded cationic nanomicelles (named as FUP) on cell viability and cell colony formation were more significant than the free UA, due to their cationic surface which can increase UA uptake by colorectal cancer cells. Cell cycle analysis showed that this inhibition effect was mediated by a cell cycle arrest at the G1 checkpoint, and the cell death induced by these nanomicelles occurred via apoptosis, which was detected by annexin V antibody and propidium iodide staining. Further western blot analysis demonstrated the apoptosis mechanism was associated with the regulation of Fas/FasL and activation of caspase-8 and caspase-3. Therefore, our cationic nanomicelles can potentially be used to enhance the therapeutic effect of UA for colorectal cancer treatment.

Prussian blue nanoparticle (PBNP), a new type of theranostic nanomaterial, had been used for cancer magnetic resonance imaging and photothermal therapy. However, their long-term toxicity after short exposure in vivo was still unclear. In this study, we investigated the dynamic changes of the biochemical and immunity indicators of mice after PBNPs injection through tail vein. Histological results showed that the PBNPs were mainly accumulated in liver and spleen. In the spleen, we found the frequency of T cells was starting to decrease after 1 day of PBNPs injection, but then slowly recovered to normal level after 60 days of injection. Meanwhile, the frequency of T cells in the blood was firstly decreased after the PBNPs injection, and then the T cell frequency kept increasing and recovered back to normal levels after 7 days of injection. The serum indexes of liver functions (alanine transaminase, aspartate transaminase, total bilirubin, and alkaline phosphatase) increased rapidly to a relatively high level only after 1 h of injection, which meant certain acute liver damage, but these indexes were gradually decreased to normal levels after 60 days of injection. These results indicate that PBNPs have acute toxicity in vivo, however, their long-term toxicity after short-time exposure is low, which might provide guidance for further applications of PBNPs in future.

Multifunctional nanomaterials with the magnetic resonance imaging (MRI) guided tumor photothermal ablation ability have been extensively applied in biomedical research as one of the most exciting and challenging strategies for cancer treatment. Nevertheless, most of these nanomaterials still suffer from low accumulation in tumor tissues and insufficient photothermal ablation of tumors so far. Here, we report a novel approach to overcome these limitations using a core-shell magnetite nanocluster@poly(dopamine)-PEG@ICG nanobead compositing of magnetite nanocluster core with coating of poly(dopamine), then further conjugating with polyethylene glycol (PEG) and adsorbing indocyanine green (ICG) on the surface. The adsorbed ICG in the nanobead displays a higher photostability and photothermal conversion ability than free ICG, as well as additional photothermal effect rather than magnetite nanocluster and poly(dopamine), which endow the nanobead with enhanced photothermal killing efficiency against cancer cells under near-infrared (NIR) laser irritation. Furthermore, it is proved that these nanobeads have excellent biocompatibility, T2-weighted MR imaging and magnetic field targeting ability. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced accumulation is observed at tumor site as proved by a darker T2-weighted MR image. Utilizing the magnetic targeting strategy, enhanced photothermal tumor ablation was achieved under laser irradiation in vivo, which is reflected by the degree of tumor tissue damage and tumor growth delay. Therefore, this nanobead integrates the abilities of magnetic field-targeting, MR imaging and photothermal cancer therapy, and might be a promising theranostic platform for tumor treatment.

Prussian Blue-based nanoparticles have been explored as the new generation of NIR-driven photothermal conversion agents (PTCAs) for cancer treatment. However, PTT treatment alone has limited therapeutic efficiency since it could not eliminate tumor cells completely. In this paper, we synthesized Prussian Blue nanocages (PBNCs) loaded with doxorubicin (DOX) (referred to as PBNCs–DOX nanocomposites) as efficient drug delivery vehicles, combining the photothermal therapy function of Prussian Blue and the chemotherapy function of DOX to enhance the therapeutic efficiency against hepatocellular carcinoma (HCC). The prepared PBNCs–DOX nanocomposites were characterized by TEM and FT-IR spectroscopy. Fluorescence intensity (FI) measurements determined that the loading content of DOX in PBNCs was as high as 33.0 wt% and that the loading efficiency was up to 88.4%. The DOX release from the PBNCs could be triggered by the environmental pH and near infra-red (NIR) laser irradiation. An in vitro cytotoxicity assay demonstrated that the PBNCs–DOX nanocomposites had significantly higher killing efficacy against HepG2 cells in the presence of NIR irradiation, than those in the absence of NIR irradiation or those in the presence of NIR irradiation but treated with PBNCs rather than PBNCs–DOX nanocomposites. Therefore, PBNCs–DOX nanocomposites, which have integrated the photothermal therapy with the chemotherapy, might serve as promising dual-mode therapeutic agents for HCC treatment in the future.

To investigate whether ESM-1 expression change reflects the impairment of endothelial cells and rejection after kidney transplantation, ESM-1 expression was detected under various immune states in this study.Kidney transplantations were performed from BN to LEW rats. Syngenic LEW-LEW grafts were used as controls. The LEW recipient rats were divided into acute rejection (AR) group, ciclosporin A (CsA) group and control group. In each group, 10 rats were sacrificed at 1, 5, and 7d after operation, respectively, and blood and kidney samples were collected. In the rat model of kidney transplantation, ESM-1 mRNA and ESM-1 protein expression were detected in various immune states to verify if ESM-1 can reflect endothelial cell impairment sensitively.ESM-1 mRNA (1d vs. 3d, P0.01;3d vs. 7d, P=0.018) and ESM-1 protein expression was upregulated significantly in the AR group (P0.01, 5 and 7d), when compared to CsA group and control group. In CsA group, the cell apoptosis rate decreased when compared to AR group (P0.01). Pathological impairment was more serious in AR group than in CsA group (P0.01).Peripheral blood ESM-1 mRNA and ESM-1 protein expression in kidney grafts can reflect the severity of endothelial cell impairment. Thus, ESM-1 may be used as a new indicator for AR prediction and diagnosis. Nevertheless, further investigation is required to test if it meets the criteria for clinical utility.

In the study, nanoporous array anodic alumina (NAAA) prepared by a simple, rapid and stable two-step anodic oxidization method was introduced as a novel solid-phase microextraction (SPME) fiber coating. The regular nanoporous array structure and chemical composition of NAAA SPME fiber coating was characterized and validated by scanning electron microscopy and energy dispersive spectroscopy, respectively. Compared with the commercial polydimethylsiloxane (PDMS) SPME fiber coating, NAAA SPME fiber coating achieved the higher enrichment capability (1.7–4.7 folds) for the mixed standards of volatile organic compounds (VOCs). The selectivity for volatile alcohols by NAAA SPME fiber coating demonstrated an increasing trend with the increasing polarity of alcohols caused by the gradually shortening carbon chains from 1-undecanol to 1-heptanol or the isomerization of carbon chains of some typical volatile alcohols including 2-ethyl hexanol, 1-octanol, 2-phenylethanol, 1-phenylethanol, 5-undecanol, 2-undecanol and 1-undecanol. Finally, NAAA SPME fiber coating was originally applied for the analysis of biological VOCs of Bailan flower, stinkbug and orange peel samples coupled with gas chromatography–mass spectrometry (GC–MS) detection. Thirty, twenty-seven and forty-four VOCs of Bailan flower, stinkbug and orange peel samples were sampled and identified, respectively. Moreover, the contents of trace 1-octanol and nonanal of real orange peel samples were quantified for the further method validation with satisfactory recoveries of 106.5 and 120.5%, respectively. This work proposed a sensitive, rapid, reliable and convenient analytical method for the potential study of trace and small molecular biological VOCs by the novel NAAA SPME fiber coating.

Background Bladder transitional cell carcinoma greatly threatens human health all over the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including bladder cancer. However, adenovirus-mediated TRAIL expression still showed cytotoxicity to normal cells mainly due to lack of tumor specificity. Methods To solve the problem, we applied miRNA response elements (MREs) of miR-1, miR-133 and miR-218 to confer TRAIL expression with specificity to bladder cancer cells. Results Expression of miR-1, miR-133 and miR-218 was greatly decreased in bladder cancer than normal bladder tissue. Luciferase assay showed that application of the 3 MREs was able to restrain exogenous gene expression to within bladder cancer cells. Subsequently, we constructed a recombinant adenovirus with TRAIL expression regulated by MREs of miR-1, miR-133 and miR-218, namely Ad-TRAIL-MRE-1-133-218. qPCR, immunoblotting and ELISA assays demonstrated that Ad-TRAIL-MRE-1-133-218 expressed in bladder cancer cells, rather than normal bladder cells. The differential TRAIL expression also led to selective apoptosis-inducing and growth-inhibiting effect of Ad-TRAIL-MRE-1-133-218 on bladder cancers. Finally, bladder cancer xenograft in mouse models further confirmed that Ad-TRAIL-MRE-1-133-218 effectively suppressed the growth of bladder cancers. Conclusions Collectively, we demonstrated that MREs-based TRAIL delivery into bladder cancer cells was feasible and efficient for cancer gene therapy.

A novel alumina nanowire (ANW) solid-phase microextraction (SPME) fiber coating was prepared by a simple and rapid anodization-chemical etching method for ultra-selective determination of volatile esters and alcohols from complicated food samples. Preparation conditions for ANW SPME fiber coating including corrosion solution concentration and corrosion time were optimized in detail for better surface morphology and higher surface area based on scanning electron microscope (SEM). Under the optimum conditions, homogeneous alumina nanowire structure of ANW SPME fiber coating was achieved with the average thickness of 20 μm around. Compared with most of commercial SPME fiber coatings, ANW SPME fiber coatings achieved the higher extraction capacity and special selectivity for volatile esters and alcohols. Finally, an efficient gas sampling technique based on ANW SPME fiber coating as the core was established and successfully applied for the ultra-selective determination of trace volatile esters and alcohols from complicated banana and fermented glutinous rice samples coupled with gas chromatography/mass spectrometry (GC/MS) detection. It was interesting that 25 esters and 2 alcohols among 30 banana volatile organic compounds (VOCs) identified and 4 esters and 7 alcohols among 13 identified VOCs of fermented glutinous rice were selectively sampled by ANW SPME fiber coatings. Furthermore, new analytical methods for the determination of some typical volatile esters and alcohols from banana and fermented glutinous rice samples at specific storage or brewing phases were developed and validated. Good recoveries for banana and fermented glutinous rice samples were achieved in range of 108-115% with relative standard deviations (RSDs) of 2.6-6.7% and 80.0-91.8% with RSDs of 0.3-1.3% (n=3), respectively. This work proposed a novel and efficient gas sampling technique of ANW SPME which was quite suitable for ultra-selectively sampling trace volatile esters and alcohols from complicated food samples.

ZnO nanorod array coating is a novel kind of solid-phase microextraction (SPME) fiber coating which shows good extraction capability due to the nanostructure. To prepare the composite coating is a good way to improve the extraction capability. In this paper, the ZnO nanorod array polydimethylsiloxane (PDMS) composite SPME fiber coating has been prepared and its extraction capability for volatile organic compounds (VOCs) has been studied by headspace sampling the typical volatile mixed standard solution of benzene, toluene, ethylbenzene and xylene (BTEX). Improved detection limit and good linear ranges have been achieved for this composite SPME fiber coating. Also, it is found that the composite SPME fiber coating shows good extraction selectivity to the VOCs with alkane radicals.

Adenoviral vectors are widely used for cancer therapy and show a tumor-suppressing effect. However, bladder cancers are found to be resistant against infection of Ad5-derived adenoviral vector, limiting the application of the existing strategy of gene therapy. Therefore, efforts to develop novel types of adenoviral vector aimed for improving the viral infection and enhancing expression level of tumor-inhibiting transgene is urgently required. We constructed a 5/35 fiber-modified E1A-deleted adenoviral vector armed with TRAIL gene. Its ability to express this gene for inhibition of bladder cancer cell growth was investigated in our work. The results showed that this modification in fiber region facilitates adenoviral infection to bladder cancer, perhaps due to high expression of CD46 on target cell surface. Subsequently, we found an enhanced expression level of TRAIL mediated by 5/35 fiber-modified adenoviral vectors in bladder cancer cells, leading to an increased tumor-inhibiting capability of 5/35 adenoviral vector against bladder cancer cells. Consistently, growth of xenograft tumors in mice was also effectively inhibited by 5/35 fiber-modified vector-mediated gene therapy strategy. The 5/35 fiber-modified adenoviral vector-based gene transfer shows an improved efficacy against bladder cancers. The application of this novel gene therapy vector may benefit the patients in clinical bladder cancer treatment.