Choi Soo-Jin, Oh Jae-Min, Choy Jin-Ho
Center for Intelligent Nano-Bio Materials, Division of Nano Sciences BK21, Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
J Inorg Biochem. 2009 Mar;103(3):463-71. doi: 10.1016/j.jinorgbio.2008.12.017. Epub 2009 Jan 9.
Many researches have shown that anionic clays can be used as delivery carriers for drug or gene molecules due to their efficient cellular uptake in vitro, and enhanced permeability and retention effect in vivo. It is, therefore, highly required to establish a guideline on their potential toxicity for practical applications. The toxicity of anionic clay, layered metal hydroxide nanoparticle, was evaluated in two human lung epithelial cells, carcinoma A549 cells and normal L-132 cells, and compared with that in other human cancer cell lines such as cervical adenocarcinoma cells (HeLa) and osteosarcoma cells (HOS). The present nanoparticles showed little cytotoxic effects on the proliferation and viability of four cell lines tested at the concentrations used (<250 microg/ml) within 48 h. However, exposing cancer cells to high concentrations (250-500 microg/ml) for 72 h resulted in an inflammatory response with oxidative stress and membrane damage, which varied with the cell type (A549>HOS>HeLa). On the other hand, the toxicity mechanism seems to be different from that of other inorganic nanoparticles frequently studied for biological and medicinal applications such as iron oxide, silica, and single walled carbon nanotubes. Iron oxide caused cell death associated with membrane damage, while single walled carbon nanotube induced oxidative stress followed by apoptosis. Silica triggered an inflammation response without causing considerable cell death for both cancer cells and normal cells, whereas layered metal hydroxide nanoparticle did not show any cytotoxic effects on normal L-132 cells in terms of inflammation response, oxidative stress, and membrane damage at the concentration of less than 250 microg/ml. It is , therefore, highly expected that the present nanoparticle can be used as a efficient vehicle for drug delivery and cancer cell targeting as well.
许多研究表明,由于阴离子粘土在体外具有高效的细胞摄取能力,以及在体内具有增强的渗透和滞留效应,因此可作为药物或基因分子的递送载体。因此,迫切需要针对其实际应用中的潜在毒性制定指导方针。在两种人肺上皮细胞(癌A549细胞和正常L-132细胞)中评估了阴离子粘土(层状金属氢氧化物纳米颗粒)的毒性,并与其他人类癌细胞系(如宫颈腺癌细胞(HeLa)和骨肉瘤细胞(HOS))进行了比较。在所使用的浓度(<250μg/ml)下,本纳米颗粒在48小时内对所测试的四种细胞系的增殖和活力几乎没有细胞毒性作用。然而,将癌细胞暴露于高浓度(250-500μg/ml)72小时会导致炎症反应,并伴有氧化应激和膜损伤,这种损伤因细胞类型而异(A549>HOS>HeLa)。另一方面,其毒性机制似乎与其他常用于生物和医学应用的无机纳米颗粒(如氧化铁、二氧化硅和单壁碳纳米管)不同。氧化铁导致与膜损伤相关的细胞死亡,而单壁碳纳米管诱导氧化应激,随后引发细胞凋亡。二氧化硅引发炎症反应,但对癌细胞和正常细胞均未造成相当程度的细胞死亡,而层状金属氢氧化物纳米颗粒在浓度低于250μg/ml时,在炎症反应、氧化应激和膜损伤方面对正常L-132细胞未显示任何细胞毒性作用。因此,人们高度期望本纳米颗粒能够用作高效的药物递送载体以及癌细胞靶向载体。