The drug delivery by versatile types of self-assembled micelles for tumor treatment, which improved the diagnostic and therapeutic effectiveness, is advocated. However, despite the numerous advantages, applications of most micelle system have been retarded by low in vivo bio-stability which led to premature drug release and nonspecific tissue accumulation. To date, a range of chemistries has been introduced in intermolecular non-covalent/covalent crosslinking strategies for these dynamic nanostructures to produce robust functional nanoparticles with enhanced circulation stability and lower non-targeted organ toxicity. In this review, we focused on recent developments in crosslinking polymeric nanoparticles in cancer therapy. Types of chemistries used in the crosslinking strategies of the micelles are outlined and their enhanced drug delivery abilities are discussed.

The perioperative glial cell line-derived neurotrophic factor levels in patients with postoperative cognitive dysfunction were lower than in patients without postoperative cognitive dysfunction. Glial cell line-derived neurotrophic factor could be an effective predictor for the occurrence of postoperative cognitive dysfunction. The results reveal a potentially important role of decreased glial cell line-derived neurotrophic factor levels in postoperative cognitive dysfunction, with possible treatment targets.

Abstract:Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to investigate the metabolic profiles of FR429 in rats in vivo. Using liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS n -IT-TOF), total eight metabolites were found in rat bile and urine after intravenous administration of FR429, but could not be detected in plasma. These metabolites were ellagic acid, mono-methylated FR429, ellagic acid methyl ether glucuronide, ellagic acid methyl ether diglucuronide, ellagic acid dimethyl ether glucuronide, and ellagic acid dimethyl ether diglucuronide. It was concluded that methylation and subsequent glucuronidation were the major metabolic pathways of FR429 in rats in vivo. This is the first report on the in vivo metabolism of the purified ellagitannin in rats.

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a 郑州大学药学院 郑州 450001) (b 新药创制与药物安全性评价河南省协同创新中心 郑州 450001) (c 河南省药物质量评价重点实验室 郑州 450001) (d 教育部药物制备关键技术重点实验室 郑州 450001) 摘要 为了寻找高效的抗肿瘤药物, 设计并合成了一系列含苯并噻唑砌块的 2,4,6-三取代嘧啶衍生物. 采用噻唑蓝 (MTT)法对目标化合物在人类四种癌细胞[EC-109(人食管癌细胞)、MGC-803(人胃癌细胞)、PC-3(人前列腺癌细胞)、 HepG-2(人肝癌细胞)]、GES-1(人正常胃黏膜上皮细胞)和 HEEC(人正常食管细胞)中进行抗肿瘤活性评价, 结果显示部 分化合物对 MGC-803 和 PC-3 细胞表现出中度至强效的抗肿瘤活性. 其中 2-(((4-(4-(吡啶-2-基)哌嗪-1-基)-6-(三氟甲基) 嘧啶-2-基)硫基)甲基)苯并[d]噻唑(13h)和 2-(((4-(4-(嘧啶-2-基)哌嗪-1-基)-6-(三-氟甲基)嘧啶-2-基)硫代)甲基)苯并[d]噻 唑(13i)对 PC-3 表现出比较好的抗肿瘤活性, IC 50 值分别 3.82 和 2.29 μmol/L, 且化合物 13h 和 13i 对 GES-1 的细胞增值 毒性明显小于阳性对照 5-氟尿嘧啶.