Eradication of unresectable liver metastasis through induction of tumour specific energy depletion.

Treatment of liver metastasis experiences slow progress owing to the severe side effects. In this study, we demonstrate a strategy capable of eliminating metastatic cancer cells in a selective manner. Nucleus-targeting W18O49 nanoparticles (WONPs) are conjugated to mitochondria-selective mesoporous silica nanoparticles (MSNs) containing photosensitizer (Ce6) through a Cathepsin B-cleavable peptide. In hepatocytes, upon the laser irradiation, the generated singlet oxygen species are consumed by WONPs, in turn leading to the loss of their photothermally heating capacity, thereby sparing hepatocyte from thermal damage induced by the laser illumination. By contrast, in cancer cells, the cleaved peptide linker allows WONPs and MSNs to respectively target nucleus and mitochondria, where the therapeutic powers could be unleashed, both photodynamically and photothermally. This ensures the energy production of cancer cells can be abolished. We further assess the underlying molecular mechanism at both gene and protein levels to better understand the therapeutic outcome

Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy

Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource

Nuclei micro-array FISH, a desirable alternative for MCL diagnosis

Mantle cell lymphoma (MCL) is a rare, specific lymphoma subtype. Though the morphologic and immunophenotypic features of MCL have been well described in recent literatures, it is still a diagnostic dilemma because of its frequent confusion with other small B cell lymphomas (SBCLs). In the present study, we primarily focus on establishing a sensitive and specific method for the diagnosis of MCL, which is efficient to distinguish this disease from other SBCLs. We carried out our investigation for MCL and other SBCLs (including SLL, FL, MZL, and MALT) on their feature of morphology, immunophenotype, and t(11;14)(q13;q32) translocation analysis based on polymerase chain reaction (PCR) and interphase nuclei micro-array fluorescence in situ hybridization (FISH). The morphologic and immunologic analysis showed the positive rate of cyclin D1 was 76.47% in MCL, which was significantly higher than that in other SBCLs. The positive rate of t(11;14) translocation was 25.81% and 35.48%, respectively, tested by general and semi-nested PCR, while 93.10% positive rate was shown with low background and strong signals pattern when tested by Nuclei micro-array FISH. Our research shows that t(11;14) translocation is a special and useful diagnostic marker for MCL, and detection of the marker by nuclei micro-array FISH is convenient and economic, especially more sensitive and specific than other methods for the diagnosis of MCL

Process Optimization and Physicochemical Characteristics Analysis of Soluble Dietary Fiber from Corn Bran Modified by Composite Enzymes

To investigate the optimal extraction process and functional characteristics of soluble dietary fiber (SDF) from corn bran. This study used corn bran, a by-product of corn processing, as raw material to extract soluble dietary fiber from corn bran through composite enzyme modification. The optimal process parameters were determined through single factor experiments and response surface methodology optimization, and their physicochemical properties were studied. The results showed that the extraction yield of SDF reached the highest value of 16.64%±0.21% when the content of cellulase was 1.5%, the content of xylanase was 1%, the enzymolysis temperature was 55 ℃ and enzymolysis time was 150 min. Its solubility was 87.63%±0.43%, the holding water capacity was 2.87±0.16 g/g, the oil holding capacity was 2.30±0.12 g/g, the glucose adsorption capacity was 5.32±0.12 mmol/g. Under simulated stomach (pH2.0) and intestinal environment (pH7.0), cholesterol adsorption capacity was 11.74±0.15 and 42.93±0.08 mg/g and sodium cholacte adsorption capacity was 15.43±0.17 and 50.67±0.10 mg/g, respectively. The research results can provide theoretical reference for the development and utilization of soluble dietary fiber from corn bran

Comparative studies of salinomycin-loaded nanoparticles prepared by nanoprecipitation and single emulsion method

To establish a satisfactory delivery system for the delivery of salinomycin (Sal), a novel, selective cancer stem cell inhibitor with prominent toxicity, gelatinase-responsive core-shell nanoparticles (NPs), were prepared by nanoprecipitation method (NR-NPs) and single emulsion method (SE-NPs). The gelatinase-responsive copolymer was prepared by carboxylation and double amination method. We studied the stability of NPs prepared by nanoprecipitation method with different proportions of F68 in aqueous phase to determine the best proportion used in our study. Then, the NPs were prepared by nanoprecipitation method with the best proportion of F68 and single emulsion method, and their physiochemical traits including morphology, particle size, zeta potential, drug loading content, stability, and in vitro release profiles were studied. The SE-NPs showed significant differences in particle size, drug loading content, stability, and in vitro release profiles compared to NR-NPs. The SE-NPs presented higher drug entrapment efficiency and superior stability than the NR-NPs. The drug release rate of SE-NPs was more sustainable than that of the NR-NPs, and in vivo experiment indicated that NPs could prominently reduce the toxicity of Sal. Our study demonstrates that the SE-NPs could be a satisfactory method for the preparation of gelatinase-responsive NPs for intelligent delivery of Sal

Reversion of pH-Induced Physiological Drug Resistance: A Novel Function of Copolymeric Nanoparticles

The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this “pH-induced physiological drug resistance” (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion.As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo.<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects.The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect

Shape Effects of Cylindrical versus Spherical Unimolecular Polymer Nanomaterials on in Vitro and in Vivo Behaviors

To date, how the shape of nanomaterials influences their biological properties is poorly understood, due to the insufficient controllability of current preparative methods, especially in the shape and size of nanomaterials. In this paper, we achieved the precise syntheses of nanoscale unimolecular cylindrical polymer brushes (CPBs) and spherical polymer nanoparticles (SPNPs) with the same volume and surface chemistry, which ensured that shape was essentially the only variable when their biological performance was compared. Accurate shape effects were obtained. Impressively, the CPBs had remarkable advantage in tissue penetration over the SPNPs. The CPBs also exhibited higher cellular uptake and rapider body clearance than the SPNPs, whereas the SPNPs had longer blood circulation time, rapider tumor vascular extravasation, and higher tumor accumulation than the CPBs. Additionally, this work also provided a controllable synthesis strategy for nanoscale unimolecular SPNPs by integrating 21 CPBs to a β-cyclodextrin core, whose diameter in dry state could be up to 45 nm

Competition between High-Speed Rail and Airline Based on Game Theory

The coexistence of high-speed rail (HSR) and airline in a busy transportation corridor generates competition between the two transportation modes. An unfair competition between HSR and airline not only reduces both revenues, but also triggers a series of social problems. Based on generalized costs, this paper proposes combining an improved gray prediction model, modified gravity model, and Logit model to predict the average passenger flow, induced passenger flow, and transfer passenger flow. According to the predicted results, we establish a game model that considers different stages of the HSR development. For demonstrative purposes, the approach is applied to an empirical study in China, that is, the competition between Beijing-Shenyang HSR and airline. Malignant fare war will make both parties lose out. Either mode that improves service quality will generate more revenue. If both parties improve the level of service, all incomes of the HSR, airline, and community increase. Results show the HSR contribution is greater than the airline in the case study