碳包铁纳米晶结合表阿霉素对HepG-2细胞的作用及对小鼠急性毒性实验研究

目的 观察单纯碳包铁纳米晶(CCIN)粒子及结合表阿霉素(EADM)的CCIN粒子对肝癌细胞的体外作用,并比较单纯EADM与结合了EADM的CCIN对小鼠的急性毒性反应.方法 MTT法检测单纯CCIN以及载EADM的CCIN对HepG-2细胞的毒性,并在光镜、电镜下观察肿瘤细胞对CCIN的吞噬作用.经尾静脉注入不同浓度药物,比较单纯EADM与EADM-CCIN混悬液对小鼠的急性毒性反应.结果 光镜、电镜下可见HepG-2细胞吞噬大量CCIN粒子人胞浆,细胞结构完整,未见明显结构破坏.各浓度的CCIN悬液(包括空白对照组)作用于HepG-2细胞系,所得的吸光度值各组间无差异.单纯EADM对HepG-2细胞株的抑制率比相应浓度的CCIN-EADM混合物高,且含CCIN量比例较低的药物组对HepG-2细胞株的抑制率要高于含CCIN量比例相对较高的组.小鼠急性毒性实验中.单纯EADM经静脉给药的LD50值为16.9 mg/kg,低于相应的EADM-CCIN混悬液的LD50值(20.7 mg/kg).结论 HepG-2细胞可吞噬CCIN粒子;在一定浓度下单纯CCIN对HepG-2细胞无毒性;载药CCIN对肿瘤细胞的抑制在短时间内较单纯相同浓度EADM的抑制作用弱,且随CCIN比例升高抑制作用相应下降;小鼠急性毒性实验中,EADM-CCIN混悬液的急性毒性相对于同剂量的单纯EADM有所降低.

Effects of carbon-coated iron nanocrystals combined with epirubicin on HepG-2 cells and its acute toxicity in mice

OBJECTIVE: To assess the cytotoxicity of carbon-coated iron nanoparticles (CCIN) and epirubicin-loaded CCIN on Hep-G2 cells in vitro and compare the acute toxicities of epirubicin and epirubicin-loaded CCIN in mice. METHODS: The cytotoxicities of CCIN and epirubicin-loaded CCIN on HepG2 cells were assessed using MTT assay, and the uptake of CCIN by the tumor cells was observed by optical and electron microscopy. Different doses of epirubicin and equivalent doses of epirubicin-loaded CCIN were injected intravenously in mice to compare their acute toxicities. RESULTS: Optical and electron microscopy revealed cytoplasmic uptake of CCIN in the tumor cells without obvious destruction of the cell structural integrity. Incubation of the HepG-2 cells with different concentrations of CCIN suspension did not result in significant variation in the mean absorbance. MTT assay showed reduced cytotoxicity of epirubicin-loaded CCIN in HepG2 cells as compared with that of epirubicin alone. The cell growth inhibition rate was significantly higher with epirubicin-CCIN mixture that contained a lower proportion of CCIN. In acute toxicity experiment with mice, the median lethal dose (LD(50)) of epirubicin was 16.9 mg/kg, while that of epirubicin-CCIN mixture was 20.7 mg/kg. CONCLUSION: CCIN uptake by HepG-2 cells does not cause obvious cytotoxicity in vitro within a certain concentration range, epirubicin-loaded CCIN has reduced cytotoxicity against HepG2 cells as compared with epirubicin, and the cytotoxicity of the mixture decreases with the increase in the CCIN content in the mixture. Epirubicin delivery in mixture with CCIN can reduce its acute toxicity in mice.