In vivo toxicity of cationic micelles and liposomes
In vivo toxicity of cationic micelles and liposomes
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DOI：
10.1016/j.nano.2014.08.004
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发表时间：
2015-02-01
影响因子：
5.4
通讯作者：
Roursgaard, Martin
中科院分区：
文献类型：
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作者：
Knudsen, Kristina Bram;Northeved, Helle;Roursgaard, Martin
本研究调查了由阳离子聚合物和脂质组分组成的纳米载体的毒性，所述纳米载体通常用于基因和药物递送，配制成阳离子胶束和脂质体。以10、25或100 mg/kg静脉注射大鼠，并在24或48 h后，或每隔一天三次静脉注射100 mg/kg后最后一次24 h后处死。肝、肺和脾的组织学评价、临床化学参数和血液学表明给药效果甚微。肺和脾中DNA链断裂增加。此外，在剂量反应研究中，我们发现抗氧化反应（HMOX 1）和氧化核碱基修复（OGG 1）中基因的表达水平不变，而细胞因子（IL 6，CXCL 2和CCL 2）的表达水平在肺，脾或肝中升高。结果表明，遗传毒性和基因表达的评估增加了有关纳米载体毒性的信息，而这是通过组织学和血液学无法获得的。(C)2015年，作者。爱思唯尔公司出版
This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the last of three intravenous injections of 100 mg/kg every other day. Histological evaluation of liver, lung and spleen, clinical chemistry parameters, and hematology indicated little effect of treatment. DNA strand breaks were increased in the lung and spleen. Further, in the dose response study we found unaltered expression levels of genes in the antioxidant response (HMOX1) and repair of oxidized nucleobases (OGG1), whereas expression levels of cytokines (IL6, CXCL2 and CCL2) were elevated in lung, spleen or liver. The results indicate that assessment of genotoxicity and gene expression add information on toxicity of nanocarriers, which is not obtained by histology and hematology. (C) 2015 The Authors. Published by Elsevier Inc.