纳米硒SCI论文

1）硒化合物与纳米硒粒子的毒性研究

Chapter 44, Handbook of Systems Toxicology（《系统毒理学手册》第44章），2011年3月

出版社：John Wiley & Sons      主办：美国食品及药品管理局（FDA）

2）食品与药品纳米毒性评价：纳米硒体外体内生物性质

Chapter 6, NANOTOXICITY: FROM IN VIVO AND VITRO MODELS TO HEALTH RISKS

（《纳米毒理体内体外研究模型与健康风险》第六章），2009年8月

出版社：John Wiley & Sons     主办：美国食品及药品管理局（FDA）

3）硒纳米颗粒可作为肠道p53抑制剂，减轻小鼠化疗引起的腹泻Pharmacological Research

（《药理学研究》）， 2019

出版社：Academic Press Inc.    主办国：英国            影响因子：5.893

4）4）亚硒酸钠对小鼠腹膜癌抗癌作用的药理机制Pharmacological Research 147 (2019) 104360

出版社：Academic Press Inc.     主办国：英国影响因子：5.893

5）硒纳米颗粒在产生活性氧方面比亚硒酸钠更有效，并且硒纳米颗粒在癌细胞中的过度积累产生了有效的治疗作用 FREE RADICAL BIOLOGY ADN MEDICINE（《自由基生物医学》）， 2018

出版社：Elsevier Science          主办国：美国   影响因子：6.170

6）腹腔注射硒纳米颗粒预防腹膜癌细胞生长的功效和安全性

FREE RADICAL BIOLOGY ADN MEDICINE（《自由基生物医学》）， 2014

出版社：Elsevier Science          主办国：美国                影响因子：6.170

7）纳米尺寸元素硒（纳米硒）与甲基硒半胱氨酸比较是一种具有低毒性的潜在防癌剂

TOXICOLOGICAL SCIENCES（《毒理学》）， 2008

出版社：Oxford University Press          主办国：美国           影响因子：3.7034）

8）与硒蛋氨酸比较纳米尺寸元素硒具有低毒性并且不削弱调节含硒酶能力

FREE RADICAL BIOLOGY ADN MEDICINE（《自由基生物医学》）， 2007

出版社：Elsevier Science              主办国：美国           影响因子：6.170

9）超营养水平元素硒纳米粒子（纳米硒）的硒积累和诱导脱毒酶谷胱甘肽硫转移酶的尺寸效应

INORGANIC BIOCHEMISTRY（《无机生物化学》）， 2007

出版社：Elsevier Science           主办国：美国   影响因子：3.212

10）硫代乙酰胺诱导硒充足的小鼠肝硬化显示缺乏硒补充情况下肝脏含硒酶会快速、持续畸形

TOXICOLOGY AND APPLIED PHARMACOLOGY（《毒理学和应用药理学》），2007

出版社：Academic Press           主办国：美国   影响因子：3.347

11）元素态纳米硒的亚慢毒性研究LIFE SCIENCES（《生命科学》）， 2005

出版社：Elsevier Science           主办国：英国               影响因子：3.647

12）纳米硒与亚硒酸盐短期毒性比较    作者：陈君石等   

LIFE SCIENCES（《生命科学》）， 2005

出版社：Elsevier Science           主办国：英国   影响因子：3.647

13）纳米红色元素硒增加小鼠和细胞中的含硒酶无尺寸效应

LIFE SCIENCES（《生命科学》）， 2004

出版社：Elsevier Science          主办国：英国                影响因子：3.647

14）纳米硒体外清除自由基作用

FREE RADICAL BIOLOGY AND MEDICINE（《自由基生物医学》），2003

出版社：Elsevier Science          主办国：美国    影响因子：6.170

15）中空球状硒纳米粒子及其体外抗羟自由基作用   作者：高学云等

ADVANCED MATERIALS（《先进材料》）， 2003

出版社：Wiley InterScience       主办国：美国        影响因子：27.398

16）纳米红色元素硒的生物学作用BIOFACTORS（《生物因素》）， 2001

出版社：IOS Press                     主办国：英国     影响因子：4.734

1)Toxicity of Selenium Compounds and Nano-Selenium Particles.

《硒化合物与纳米硒粒子毒理研究》

  作者张劲松

[Conclusions]

Selenium is a necessary dietary constituent of at least 25 human selenoproteins and enzymes all containing selenocysteine. Replacement of selenium by sulfur in enzymes diminishes or obfuscates catalytic activity. Replacement of selenium by sulfur in selenium analogues dramatically reduces or totally eliminates toxicity. The reverse is also true. Replacement of catalytic sulfur by selenium in sulfur compounds universally increase catalytic activity and/or toxicity. In excessive amounts, all selenium compounds become toxic is a dose-dependent fashion to cells in vitro and to the primary target tissue of chronic selenium toxicity, the liver. Nanotechnology is a rapidly developing modern technology branch dealing with materials in the nanometer-size range. With their extremely small size nanomaterials can enter cells and with their huge surface area nanomaterials have the potential to interact with intracellular macromolecules exhibiting toxicity or bioactivity. There exist obvious public safety concerns about nanomaterials. Accordingly, a new research discipline known as nanotoxicology has emerged. However, nanotechnology may also hold promise for pharmacology because nanomaterials normally exhibit novel properties different from those of both molecular and bulk materials. Elemental seleniuim has long been considered to be biologically inert. With bovine serum albumin or other dispersant agents such as polysaccharides, biologically active Nano-Se aggregates are formed from sodium selenite and glutathione. Different from the biologically inert black elemental selenium with coarse size, Nano-Se manifests toxicity whcih conforms to the concern of nanotoxicity. However, compared with selenium compounds such as sodium selenite, selenomethionine and Se-methylselenocysteine, Nano-Se is not compromised in increasing the activities of selenoenzyme and phase 2 enzyme, but exhibits much lower toxicity. Nano-Se is thus a potential selenium nutritional source with a prominent characteristic of lower toxicity for supplementation.

[摘要]

硒是人体必需的微量元素，人体中含有至少25种重要的硒蛋白和含硒酶。如果硒元素被硫元素替代，相应生物酶的催化活性就会减少或者发生混淆。同时也会大幅度降低或完全消除毒性。反过来也一样。用硒元素替代硫化合物中的硫元素，催化活性普遍提高，毒性亦然。过量条件下，所有的硒化合物产生毒性都是有剂量依赖效应的，不论是体外细胞还是主要目标组织的慢性硒毒性，比如肝脏。纳米技术是一个飞速发展的当代技术分支，是在纳米尺寸范围对物质进行处理的科学。体积非常微小的纳米材料进入细胞，他们具有巨大的表面积，使得纳米材料有潜在可能性与细胞内大分子相互作用，显示出毒性和生物活性。因此对纳米材料就存在着明显的公共安全方面的担忧。因此，出现了一个新的研究学科——纳米毒理学。然而，纳米技术也可能给药理学带来希望，因为纳米材料通常表现出不同于微观分子或者宏观物质两方面的新颖性质。元素硒一直被认为生物惰性。以蛋白或者多糖作为分散剂，亚硒酸钠还原制备出具有生物活性的纳米元素硒Nano-Se。不同于宏观尺度的生物惰性黑色元素硒，Nano-Se体现出纳米毒理学所担忧的毒性。但是，与其它硒化合物相比，如亚硒酸钠、蛋氨酸和甲基硒半胱氨酸等，Nano-Se在同等调节含硒酶以及二相酶活性上升时显示出更低的毒性。因此，Nano-Se具有的明显低毒性表明它可以作为营养补充剂的硒源。

2)Evaluation of Nanotoxicity of Foods and Drugs: Biological Properties

of Red Elemental Selenium at Nano Size (Nano-Se) In Vitro and In Vivo

《食品与药品纳米毒理评价：纳米硒体外体内生物性质》   

  作者：张劲松

[Summary]

Nanotechnology holds promise for medication and nutrition because material at nanometer dimensions exhibits novel properties different from those of both isolated atoms and bulk material. Elemental selenium in the redox state of zero in general is considered to be biologically inert. With a certain protein as a disperser, neonatal elemental selenium atoms generated via reducing sodium selenite with glutathione can aggregate into Nano-Se. In contrast to biologically inert black elemental selenium at micrometer size, Nano-Se indeed manifests toxicity, which conforms to the notion that nanoparticles increase health risks. On the other hand, selenium is an essential trace element with a narrow margin between necessary intake amount and toxicity, whereas cancer-preventive effects of selenium were mostly observed at high doses in animals. For nutritional supplementation and cancer prevention, the optimal selenium form is expected to possess high biological activity and low toxicity. Compared with sodium selenite, selenomethionine or Se-methylselenocysteine, Nano-Se possesses equal efficacy in increasing the activities of selenoenzymes, but has much lower toxicity. These results suggest that Nano-Se can be considered as a novel selenium source with a reduced risk of selenium toxicity.

[摘要]

纳米技术为医学和营养学发展带来新的前景，因为纳米尺寸颗粒既不同于独立的原子又不同于块体材料，会出现新特性。通常情况下，零价态硒被认为没有生物学性质。使用特定的蛋白质作为分散剂，谷胱甘肽还原亚硒酸钠生成的新生零价态硒原子聚集成为纳米颗粒，即纳米硒。与没有生物活性的微米尺寸黑色元素硒相比，纳米硒确实产生了毒性，这与广泛的共识相一致，即纳米粒子可能具有健康风险。另一方面，硒作为人体必需的微量元素，它的毒性剂量和所需的营养剂量之间范围很窄，而动物实验发现，高剂量硒在癌症预防时效果更确切。对于营养补充和癌症预防，最理想的硒形式是具有高活性的同时毒性较低。与亚硒酸钠、硒蛋氨酸、硒甲基半胱氨酸这些国内外广泛使用的无机硒或有机硒相比，纳米硒拥有与他们相同的增强含硒酶的能力，但是，纳米硒的毒性最低。这些结果表明纳米硒可以作为一种安全性高的新型硒源。

3)Selenium nanoparticles act as an intestinal p53 inhibitor mitigating

chemotherapy-induced diarrhea in mice. Pharmacological Research 149 (2019) 104475

论文标题：硒纳米颗粒可作为肠道p53抑制剂，减轻小鼠化疗引起的腹泻

[ABSTRACT]

Selenium, at high-dose levels approaching its toxicity, protects tissues from dose-limiting toxicities of many cancer chemotherapeutics without compromising their therapeutic effects on tumors, there by allowing the delivery of higher chemotherapeutic doses to achieve increased cure rate. In this regard, selenium nanoparticles (SeNPs), which show the lowest toxicity among extensively investigated selenium compounds including methylselenocysteine and selenomethionine, are more promising for application. The key issue remains to be resolved is whether low-toxicity SeNPs possess a selective protective mechanism. p53 or p53-regulated thrombospondin-1 has each been confirmed to be an appropriate target for therapeutic suppression to reduce side effects of anticancer therapy. The present study demonstrated that SeNPs transiently suppressed the expression of many intestinal p53-associated genes in healthy mice. SeNPs did not interfere with tumor-suppressive effect of nedaplatin, a cisplatin analogue; however, effectively reduced nedaplatin-evoked diarrhea. Nedaplatin-induced diarrhea was associated with activation of intestinal p53 and high expression of intestinal thrombospondin-1. The preventive effect of SeNPs on nedaplatin-induced diarrhea was correlated with a powerful concomitant suppression of p53 and thrombospondin-1. Moreover, the high-dose SeNPs used in the present study did not suppress growth nor caused liver and kidney injuries as well as alterations of hematological parameters in healthy mice. Overall, the present study reveals that chemotherapeutic selectivity conferred by SeNPs involves a dual suppression of two well-documented targets, the p53 and thrombospondin-1, providing mechanistic and pharmacologic insights on low-toxicity SeNPs as a potential chemoprotectant for mitigating chemotherapy-induced diarrhea.

4)Pharmacological mechanisms of the anticancer action of sodium selenite against peritoneal cancer in mice. Pharmacological Research 147 (2019) 104360

论文标题：亚硒酸钠对小鼠腹膜癌抗癌作用的药理机制

[ABSTRACT]

Peritoneal carcinomatosis has an extremely poor overall prognosis and remains one of the greatest oncologic challenges. Prior studies in mice show that sodium selenite administered intraperitoneally is highly effective in inhibiting cancer cells implanted in the peritoneal cavity. However, the pharmacological mechanism remains unclear. The present study revisited the therapeutic effect of selenite and elucidated its mechanism of action. We found that intraperitoneal delivery of selenite to cancer cells in the peritoneal cavity of mice rapidly and robustly killed the cancer cells, with a therapeutic efficacy higher than that of cisplatin. The action of selenite was associated with the following pharmacological mechanisms. 1) Favorable drug distribution: selenite increased selenium levels in the cancer cells by 250-fold, while in normal tissues only by 7-fold. 2) Optimal selenium form: selenite was converted in the cancer cells mainly into selenium nanoparticles (SeNPs), which are more efficient than selenite in producing reactive oxygen species (ROS). 3) Persistent hijacking of two pro-survival systems to generate ROS: selenite did not impair thioredoxin- and glutaredoxin-coupled glutathione systems, which facilitate SeNPs to generate ROS and caused severe organelle injury and apoptotic response in the cancer cells. Overall, these mechanisms tend to maximize the potential of selenite in producing ROS in cancer cells and underlie selenite as a candidate therapeutic agent for peritoneal carcinomatosis.

5)Selenium nanoparticles are more efficient than sodium selenite in producing reactive oxygen species and hyper-accumulation of selenium nanoparticles in cancer cells generates potent therapeutic effects. Free Radical Biology and Medicine 126 (2018) 55–66

论文标题：硒纳米颗粒在产生活性氧方面比亚硒酸钠更有效，并且硒纳米颗粒在癌细胞中的过度积累产生了有效的治疗作用

[ABSTRACT]

We have previously demonstrated that selenium nanoparticles (SeNPs) administered via oral route possess similar capacities of increasing selenoenzyme activities as the extensively examined sodium selenite, selenomethionine and methylselenocysteine, and yet display the lowest toxicity among these selenium compounds in mouse models. However, the low toxicity of SeNPs found in mammalian systems would lead to the interpretation that the punctate distribution of elemental selenium found in cultured cancer cells subjected to selenite treatment that triggers marked cytotoxicity represents a detoxifying mechanism. The present study found that SeNPs could be reduced by the thioredoxin- or glutaredoxin-coupled glutathione system to generate ROS. Importantly, ROS production by SeNPs in these systems was more efficient than by selenite, which has been recognized as the most redox-active selenium compound for ROS production. This is because multiple steps of reduction from selenite to selenide anion are required; whereas only a single step reduction from the elemental selenium atom to selenide anion is needed to trigger redox cycling with oxygen to produce ROS. We thus speculated that accumulation of SeNPs in cancer cells would result in a strong therapeutic effect, rather than serves a detoxification function. Indeed, we showed herein that preformed SeNPs generated a potent therapeutic effect in a mouse model due to rapid, massive and selective accumulation of SeNPs in cancer cells. Overall, for the first time, we demonstrate that SeNPs have a stronger pro-oxidant property than selenite and hyper-accumulation of SeNPs in cancer cells can generate potent therapeutic effects.