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标题: 氧化铈纳米颗粒可改善肝细胞癌的预后 [打印本页]

作者: StephenW 时间: 2020-2-11 11:08 标题: 氧化铈纳米颗粒可改善肝细胞癌的预后

Cerium oxide nanoparticles may improve hepatocellular carcinoma prognosis

by Catalan Institute of Nanoscience and Nanotechnology

                           Cerium oxide nanoparticles nanoparticles. Credit: Catalan Institute of Nanoscience and Nanotechnology

Hepatocellular carcinoma is the most common liver cancer and ranks third in the world in terms of mortality. Its appearance is related to the hepatitis B and C viruses, alcoholism, metabolic diseases of the liver and exposure to certain toxins. Although its molecular mechanisms have been described in detail, no effective treatment is currently available after the early stages of the disease. When ablation is no longer possible, the best therapeutic approaches fail to stop the progression of the cancer. According to the journal Hepatology, this could change thanks to an experimental treatment based on cerium oxide nanoparticles on which the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2) have been jointly working for some time.
                                                                                                   The paper explains how, thanks to their antioxidant and anti-inflammatory properties, cerium oxide nanoparticles have been able to partially reverse the cellular mechanisms involved in tumor progression and have managed to significantly increase survival in a rat animal model. The last authors of the study are Prof. Wladimiro Jiménez at the Hospital Clínic of Barcelona and ICREA Prof. Víctor F. Puntes. The first author is Guillermo Fernández-Varo, member of the IDIBAPS research group mentioned above and of the CIBER on Liver and Digestive Diseases (CIBERehd).
This research began almost a decade ago and produced its first results in 2016 when IDIBAPS and ICN2 published a paper in the Journal of Hepatology. The work highlighted the anti-inflammatory therapeutic potential of cerium oxide nanoparticles for the treatment of several chronic liver diseases. The new work in Hepatology focuses on hepatocellular carcinoma and analyses the impact of the experimental treatment on a rat animal model with induced cancer, studies the distribution of the drug in three human livers discarded for transplantation and details intracellular absorption in human liver cancer cell cultures. This translational research brings the new treatment closer to the clinical phases of experimentation.
The research team injected the rats with four doses of cerium oxide nanoparticles, two per week, 16 weeks after they developed liver cancer. The spherically shaped nanoparticles, between 4 and 20 nanometers, were mainly concentrated in the liver and spleen a few days after administration. The treated rats attenuated the number of cancer nodules in the liver, had reduced levels of the cancer biomarker alpha-fetoprotein, showed less proliferation of the cancer cells and more apoptosis cell death, and had beneficial effects by reducing the damage produced by inflammation and altered lipid metabolism. When the survival of the treated rats was compared, it was observed that both the nanoparticles and the best therapeutic option available at the time of the study doubled the survival of the rats from about 15 days to over 30.
The distribution of nanoparticles in functional human livers was observed though imaging techniques in organs rejected for transplantation. In only 30 minutes, half of the nanoparticles were retained in the liver, forming agglomerates of different sizes in several locations. Cell cultures from human liver cancer also showed a high adsorption capacity of the nanoparticles after 24 hours of exposure. Therefore, treatment based on cerium oxide nanoparticles, which equaled without side effects the results of the best therapeutic option available today, could lead to an innovative pharmacological strategy for a disease in need of new therapies.

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作者: StephenW 时间: 2020-2-11 11:08

氧化铈纳米颗粒可改善肝细胞癌的预后

加泰罗尼亚纳米科学与纳米技术研究所
氧化铈纳米粒子。图片来源：加泰罗尼亚纳米科学与纳米技术研究所

肝细胞癌是最常见的肝癌，其死亡率排名世界第三。它的出现与乙型和丙型肝炎病毒，酒精中毒，肝脏的代谢性疾病以及某些毒素的暴露有关。尽管已经详细描述了其分子机制，但是在疾病的早期阶段之后目前没有有效的治疗方法。当不再可行消融时，最好的治疗方法将无法阻止癌症的进展。根据《肝病学》杂志的报道，由于基于氧化铈纳米粒子的实验性处理方法，这种情况可能会改变，在该方法上，Institut d'InvestigacionsBiomèdiquesAugust Pi i Sunyer（IDIBAPS）和加泰罗尼亚纳米科学与纳米技术研究所（ICN2）共同致力于一段时间

该论文解释了氧化铈纳米颗粒由于其抗氧化和抗炎特性，如何能够部分逆转参与肿瘤进展的细胞机制，并成功地显着提高了大鼠动物模型的存活率。该研究的最后作者是巴塞罗那医院Clínic的WladimiroJiménez教授和ICREA的VíctorF. Puntes教授。第一作者是GuillermoFernández-Varo，他是上述IDIBAPS研究小组成员以及《 CIBER肝与消化系统疾病》（CIBERehd）的成员。

这项研究始于大约十年前，并在2016年IDIBAPS和ICN2在《肝病学杂志》上发表了论文时产生了第一批结果。这项工作强调了氧化铈纳米粒子在治疗几种慢性肝病中的抗炎治疗潜力。肝病学的新工作着眼于肝细胞癌，并分析了实验治疗对诱发癌症的大鼠动物模型的影响，研究了该药物在丢弃的三个人类肝脏中的分布，并详细介绍了人类肝癌细胞培养物中的细胞内吸收。这项转化研究使新疗法更接近实验的临床阶段。

研究小组在老鼠患上肝癌后16周，每周两次给老鼠注射四剂氧化铈纳米颗粒。给药后几天，球形纳米颗粒在4至20纳米之间，主要集中在肝脏和脾脏中。经治疗的大鼠减毒了肝脏中的癌症结节数量，降低了癌症生物标志物甲胎蛋白的水平，显示出癌细胞的增殖减少，凋亡细胞死亡增加，并通过减少炎症和改变造成的损害而具有有益作用。脂质代谢。当比较被治疗大鼠的存活率时，可以观察到纳米颗粒和研究时可用的最佳治疗选择都使大鼠的存活率从约15天翻了一番，超过30天。

通过成像技术拒绝移植器官中观察到纳米粒子在功能性人类肝脏中的分布。在仅30分钟内，一半的纳米颗粒保留在肝脏中，在几个位置形成不同大小的团聚物。在暴露24小时后，来自人类肝癌的细胞培养物也显示出纳米颗粒的高吸附能力。因此，基于氧化铈纳米粒子的治疗（无副作用）相当于当今可用的最佳治疗方案的结果，可为需要新疗法的疾病带来创新的药理策略。

进一步探索
磁性纳米材料成为抗肝纤维化的有效疗法

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