中空介孔硅球对血管内皮细胞的细胞毒性

Cytotoxicity of hollow mesoporous silica nanoparticles on human umbilical vein endothelial cells

通过细胞增殖实验和乳酸脱氢酶释放实验,流式细胞术,透射电镜及电感耦合等离子体发射光谱仪检测等方法,证实HMSN在浓度超过62.5μg/mL时,会对人脐静脉血管内皮细胞产生毒性,半抑制浓度约为150μg/mL.高浓度下HMSN导致细胞增殖抑制和乳酸脱氢酶释放,使细胞周期阻滞在G1期,并最终诱导细胞坏死.同时发现HMSN粉体在细胞培养液中浸提后,其浸提液在稀释比例小于1/64时仍有毒性,同样会抑制内皮细胞的增殖,并诱导细胞坏死.HMSN的毒性可能来源于HMSN颗粒本身对细胞和亚细胞结构的物理损伤作用,以及在细胞内降解产物的化学损伤作用.因此,使用HMSN递送抗癌药物应注意控制载体单次用量,避免对正常组织血管的毒性,促进对肿瘤组织血管的破坏.

In this study the cytotoxicity caused by HMSN to human umbilical vessel endothelial cells（HUVECs） was examined by inhibition of cell proliferation,lactate dehydrogenase（LDH） release assay,flow cytometer analysis,transmission electron microscopy（TEM） and indictive coupled plasma-atomic emission spectroscopy（ICP-AES）.The results showed that HMSN at the concentration more than 62.5μg/mL will exert cytotoxicity on HUVECs and the IC50 is 150μg/mL.At high concentration HMSN significantly inhibited the proliferation of HUVECs, causing LDH release,arrest cell cycle at G1 period and eventually induced necrosis.The extracts of HMSN also had the same effect on HUVECs at different dilution ratios less than 1：64,indicating the degradation product of HMSN had cytotoxicity.The cytotoicity may come from the physical damage on cell structure by HMSN,and chemical disturbance on metabolism caused by product of HMSN degradation.Therefore,attentions should be paid on the single dosage,avoiding cytotoxicity to normal tissue vessels;stimulating cytotoxicity to tumor vessel.