首页|羟基喜树碱铁蛋白包合物的制备及其抗结肠癌活性的研究

羟基喜树碱铁蛋白包合物的制备及其抗结肠癌活性的研究

扫码查看
目的 用铁蛋白(ferritin,Fn)包合羟基喜树碱(hydroxycamptothecin,HCPT)制备羟基喜树碱铁蛋白包合物(hydroxycamptothecin@ferritin,HCPT@Fn),增加HCPT的溶解性,提高治疗结肠癌的效果。方法 用透析法制备HCPT@Fn;用激光粒度测定仪检测HCPT@Fn的粒径及Zeta电位;用超高效液相色谱法(ultra-high performance liquid chromatography,UPLC)检测HCPT@Fn 中 HCPT 的载药量;用 3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]实验、活死细胞染色实验及克隆形成实验考察HCPT@Fn对人结肠癌细胞(human colon cancer cells,HT-29)的毒性;用荧光显微镜观察HCPT@Fn在HT-29细胞内的蓄积;用溶血实验及HE染色实验初步考察HCPT@Fn的安全性。结果 用透析法制备的HCPT@Fn的粒径为148。4 nm,Zeta电位为-34。4 mV,载药量为37。46%;HCPT@Fn能大量蓄积于HT-29细胞中,可显著抑制HT-29细胞的增殖及克隆形成;在设定的质量浓度范围内,HCPT@Fn均未造成明显的溶血,HCPT@Fn对小鼠正常组织无明显破坏性。结论 HCPT@Fn能够显著增加HCPT的溶解性,提高抗结肠癌活性并降低毒性和不良反应。
Study on the preparation and anti-colon cancer activity of hydroxycamptothecin loaded ferritin inclusion complex
Objective In order to increase the solubility and improve the therapeutic effect of colon cancer,a hydroxycamptothecin(HCPT)loaded ferritin(Fn)inclusion complex(hydroxycamptothecin@ferritin,HCPT@Fn)was prepared.Methods Dialysis method was used to prepare HCPT@Fn.Then,the particle size and Zeta potential of HCPT@Fn were evaluated by laser particle size analyzer.The drug loading of HCPT@Fn was determined by ultra-high performance liquid chromatography(UPLC).The cytotoxicity of HCPT@Fn on human colon cancer cells(HT-29)cells was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,alive/dead cell staining test and clone formation assay.The uptake of HCPT@Fn in HT-29 cells was detected by fluorescence microscope.The safety of HCPT@Fn was investigated by hemolysis test and HE staining preliminarily.Results The particle size and Zeta potential of HCPT@Fn were 148.4 nm and-34.4 mV,respectively.The drug loading of HCPT in HCPT@Fn was 37.46%.HCPT@Fn can accumulate in large amounts in HT-29 cells,inhibiting the proliferation and clone formation of HT-29 cells significantly.In the set concentration range,HCPT@Fn did not cause significant hemolysis,and did not cause significant damage to normal tissue in mice.Conclusion HCPT@Fn could increase the solubility of HCPT,enhance the anti-colon cancer activity of HCPT and reduce toxic side effects.

hydroxycamptothecinferritininclusion complexcolon cancerchemotherapy

刘玉娇、杨静、罗静远、李雪、周四元、刘道洲

展开 >

空军军医大学药学系药剂学与药事管理学教研室,西安 710032

羟基喜树碱 铁蛋白 包合物 结肠癌 化疗

陕西省重点研发计划重点产业创新链项目陕西省重点研发计划一般项目

2021ZDLSF03-082023-YBSF-221

2024

西北药学杂志
西安交通大学,陕西省药学会

西北药学杂志

CSTPCD
影响因子:0.912
ISSN:1004-2407
年,卷(期):2024.39(4)