SN-38载药纳米微球对人胃癌细胞BGC-823的抑制作用

SN-38-loaded polymeric micelles can inhibit the growth of human gastric adenocarcinoma BGC-823 cells

目的:检测喜树碱活性代谢产物SN-38载药纳米微球(SN-38-np)的各项特征,比较该载药纳米微球与裸药抗人胃癌肿瘤细胞BGC-823的效果.方法:用溶剂分散法制备SN-38/PCL-PEG纳米微球.原子力显微镜和透射电子显微镜观察纳米微球形态,采用高效液相色谱法(HPLC)测定SN-38浓度并计算该载药微球载药量、包封率及描绘其体外释放曲线.采用MTT法观察该微球对人胃癌细胞株BGC-823的生长抑制效果,荧光显微镜检测细胞内活性氧(ROS)水平.结果:微球为不规则的圆形,平均粒径小于100nm.载药量11%左右,包封率80%左右;SN-38纳米微球可稳定溶解于水中且具有良好的缓释特性;MTT结果显示,较低浓度的SN-38载药纳米微球在72h抑制肿瘤效果明显优于SN-38裸药,同时计算IC50发现SN-38载药纳米微球在24h和72h的IC50明显低于SN-38裸药(P<0.05),两者48h时间点的IC50相当;细胞内活性氧(ROS)检测结果显示:裸药和载药微球均可明显诱导ROS产生,在较低作用浓度时,SN-38载药纳米微球可比裸药诱导产生更多的细胞内ROS产物.结论:SN-38载药纳米微球可使细胞内达到并维持有效药物浓度,即使在较低作用浓度下亦可持续有效的抑制肿瘤细胞生长,效果明显优于相同浓度下SN-38裸药.

AIM：To investigate the characteristics of SN38-loaded polymeric micelles and compare their inhibitory effect on human gastric adenocarcinoma BGC-823 cells with that of free SN-38.METHODS：SN-38/PCL-PEG nanoparticles （SN-38-NP） were synthesized by solvent diffusion method.The morphology of nanoparticles were detected by atomic force microscopy and transmission electron microscopy.The drug loading content,encapsulation efficiency,and in vitro release of SN-38-NP were evaluated by ultraviolet spectrophotometry and high-performance liquid chromatography （HPLC）. The effects of SN-38-NP on the proliferation of BGC-823 cells were examined by methyl thiazolyl tetrazolium （MTT） assay. The level of reactive oxygen species （ROS） was detected by dichlorofluorescein （DCF） assay.RESULTS： The average diameter of drug-loaded nanoparticles was less than 100 nm. The drug- loaded nanoparticles had higher drug loading content （about 11%） and encapsulation efficiency （about 80%） than free SN-38. SN-38 could be effectively incorporated into nanoparticles with core-shell structure to act as a water-soluble controlled release drug delivery system. The results of MTT assay showed that the half maximal inhibitory concentration （IC50） of SN-38-NP was obviously lower than that of free SN-38 at 24 and 72 h after treatment （P 〈 0.05） though there was no significant difference at 48 h. Although both free SN-38 and SN-38 nanoparticles could increase ROS production, the SN-38-NP induced more ROS at low concentrations （P 〈 0.05）. CONCLUSION： SN-38-NP could be effectively incorporated into core-shell nanoparticles to act as a water-soluble controlled release drug delivery system. SN-38-NP is superior to free SN-38 in restraining the growth of tumor cells even at low concentrations.