摘要
采用乳化溶剂挥发法制备载紫杉醇的叶酸靶向纳米胶束PTX@FA-PLGA-NMs,以纳米胶束的粒径及PDI为评价指标,优选载紫杉醇纳米胶束的工艺参数,采用透射电镜观察纳米胶束的形态,并系统考察纳米胶束的稳定性、载药量和包封率等,体外细胞实验研究纳米胶束的细胞毒作用,细胞凋亡及细胞摄取等。结果以最佳工艺制备的纳米胶束粒径为(125.3±1.2)nm,多分散系数PDI为0.086±0.026,Zeta电位为(-20.0±3.8)mV,载药量为7.2%±0.75%,包封率为50.7%±1.0%,纳米胶束在透射电镜下为规则的球形,空白纳米胶束FA-PLGA-NMs对细胞的增殖与生长几乎没有抑制作用,而载药纳米胶束与游离PTX对肿瘤细胞的增殖与生长有明显的抑制作用,且PTX@FA-PLGA-NMs的半数抑制浓度IC50为0.56μg·mL^(-1),PTX的半数抑制浓度IC50为0.66μg·mL^(-1)。细胞划痕实验显示,载紫杉醇的纳米胶束具有良好的抑制细胞迁移的能力。PTX@FA-PLGA-NMs纳米胶束具有很好的促宫颈癌HeLa细胞凋亡作用,并且能够明显促进HeLa细胞的摄取。体外实验结果均表明PTX@FA-PLGA-NMs能够实现对宫颈癌HeLa细胞的靶向及治疗的目的。因此,具有抗癌作用的PTX@FA-PLGA-NMs作为纳米药物载体是一种有潜力的提高肿瘤治疗效果的纳米系统。
The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid)nano-micelles(PTX@FA-PLGA-NMs)were prepared by the emulsion solvent evaporation method,and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes.The morphology of the nano-micelles was observed by transmission electron microscopy(TEM),and the stability,drug loading and encapsulation efficiency were systematically investigated.In vitro experiments were performed to study the cytotoxic effects of nano-micelles,apoptosis,and cellular uptake.Under the optimal parameters,the nano-micelles showed the particle size of(125.3±1.2)nm,the PDI of 0.086±0.026,the zeta potential of(-20.0±3.8)mV,the drug loading of 7.2%±0.75%,and the encapsulation efficiency of 50.7%±1.0%.The nano-micelles were in regular spherical shape as observed by TEM.The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells,while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects.The IC50 of PTX@FA-PLGA-NMs and PTX was 0.56μg·mL^(-1)and 0.66μg·mL^(-1),respectively.The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay.PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells.The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells.Therefore,as nanodrug carriers,PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.
作者
李新健
游云
张琼玲
张冰冰
严林
欧则民
张瑶
王艳静
仝燕
刘德文
王锦玉
LI Xin-jian;YOU Yun;ZHANG Qiong-ling;ZHANG Bing-bing;YAN Lin;OU Ze-min;ZHANG Yao;WANG Yan-jing;TONG Yan;LIU De-wen;WANG Jin-yu(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第10期2481-2488,共8页
China Journal of Chinese Materia Medica
基金
中国中医科学院优秀青年科技人才(创新类)项目(ZZ14-YQ-024)。
