细胞穿膜肽PFV修饰紫杉醇/青蒿琥酯共载靶向胶束的制备及体外抗肿瘤作用研究
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篇名: | 细胞穿膜肽PFV修饰紫杉醇/青蒿琥酯共载靶向胶束的制备及体外抗肿瘤作用研究 |
TITLE: | Study on Preparation and in vitro Anticancer Activity of PFV-modified Paclitaxel/artesunate Co-loaded Targeting Micelles |
摘要: | 目的:制备细胞穿膜肽PFV修饰紫杉醇(PTX)/青蒿琥酯(ART)共载靶向胶束,并考察其体外抗肿瘤活性。方法:按前期优化的工艺,采用薄膜水化法制备PFV修饰PTX/ART共载靶向胶束,并对其进行表征。以空白胶束作为空白对照,采用磺基罗丹明B法评价PTX胶束、ART胶束、PTX/ART胶束以及PFV修饰PTX/ART共载靶向胶束对人胃癌BGC-823细胞的毒性;以香豆素作为荧光探针取代PTX,制成相应的不同胶束,采用流式细胞仪和荧光显微镜测定和观察BGC-823细胞对各胶束的摄取情况和靶向性;并通过Transwell小室法考察PTX胶束、ART胶束、PTX/ART胶束以及PFV修饰PTX/ART共载靶向胶束对BGC-823细胞侵袭的影响。结果:PFV修饰PTX/ART共载靶向胶束的平均粒径为(51.30±3.95)nm,分散系数为0.19±0.01,Zeta电位为(0.21±0.02)mV,PTX、ART的包封率均高于90%,形态呈圆球形。空白胶束对BGC-823细胞无明显毒性,PTX胶束、PTX/ART胶束以及PFV修饰PTX/ART共载靶向胶束对BGC-823细胞的半数抑制浓度分别为(3.09±0.22)、(1.93±0.24)、(1.11±0.15)μmol/L;不同胶束在BGC-823细胞核中的分布数量排序依次为PFV修饰香豆素/ART胶束>香豆素/ART胶束>香豆素胶束>空白对照,抑制细胞侵袭作用的大小依次为PFV修饰PTX/ART共载靶向胶束>PTX/ART胶束>ART胶束>PTX胶束>空白对照。结论:制备的PFV修饰PTX/ART共载靶向胶束符合《中国药典》要求;其对BGC-823细胞具有较强的细胞毒性,可提高药物的靶向性和细胞对药物的摄取能力,并能抑制肿瘤细胞的侵袭和转移。 |
ABSTRACT: | OBJECTIVE:To prepare cell penetrating peptide PFV-modified paclitaxel (PTX)/artesunate(ART)co-loaded targeting micelles ,and to investigate in vitro anti-tumor activity. METHODS :According to optimal technology ,PFV-modified PTX/ ART co-loaded targeting micelles were prepared by membrane hydration method ,and were characterized. Using blank micelle as blank control ,sulforhodamine B (SRB)method was used to evaluate the toxicity of PTX micelles ,ART micelles ,PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to human gastric cancer BGC- 823 cells. The coumarin was used as fluorescent probe replacing PTX to prepare corresponding micelles. Then ,the uptake of BGC- 823 cells to corresponding micelles and targeting effect were observed and determined by flow cytometry and fluorescence microscope. The effects of PTX micelles , ART micelles ,PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles on the invasion of BGC- 823 cells were investigated by Transwell chamber method. RESULTS :Average particle size of PFV-modified PTX/ART co-loaded targeting micelles was (51.30±3.95)nm;PDI was 0.19±0.01,and Zeta potential was (0.21±0.02)mV. The encapsulation efficiency of PTX and ART were higher than 90%. The shape of micelles were spherical. The blank micelles had no obvious toxicity to BGC-823 cells. The IC 50 value of PTX micelles ,PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to BGC-823 cells were (3.09±0.22),(1.93±0.24),(1.11±0.15)μmol/L,respectively. The distribution amount of different micelles in BGC- 823 cell nucleus in the descending order were PFV-modified coumarin/ART micelles >coumarin/ART micelles >coumarin micelles>blank control. The order of inhibitory effect was PFV-modified PTX/ART co-loaded targeting micelles >PTX/ART micelles>ART micelles >PTX micelles >blank control. CONCLUSIONS: Prepared PFV-modified PTX/ART No.81874347) co-loaded targeting micelles are in line with the quality of 1915286446@qq.com Chinese Pharmacopoeia . It shows strong cytotoxicity to BGC-823 cells,can improve the drug targeting and the cell uptake,and inhibit the inv asion and metastasis of BGC- 823 cells. |
期刊: | 2020年第31卷第21期 |
作者: | 王为,李学涛,孔亮,姜爽,罗一夫,王晓波 |
AUTHORS: | WANG Wei,LI Xuetao ,KONG Liang,JIANG Shuang ,LUO Yifu,WANG Xiaobo |
关键字: | 细胞穿膜肽;紫杉醇;青蒿琥酯;胶束;人胃癌BGC-823细胞;靶向作用;抗肿瘤作用 |
KEYWORDS: | Cell-penetrating peptide ;Paclitaxel;Micelles;Artesunate;Human gastric cancer BGC- 823 cells;Targeting effects; |
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