槲皮素纳米给药系统对肿瘤细胞的生物学效应与体内安全性研究  

Biological Effects and in Vivo Safety of Quercetin Nano Drug Delivery System on Tumor Cells

作　　者：白云 孙艳雪 刘丝露 胡密霞 张可青 塔娜 崔淑侠[3] 徐鹏程 BAI Yun;SUN Yan-xue;LIU Si-lu;HU Mi-xia;ZHANG Ke-qing;TA Na;CUI Shu-xia;XU Peng-cheng(School of Pharmacy,Inner Mongolia Medical University,Hohhot O10110,China;Endoscopy Center of People's Hospital of Inner Mongolia Autonomous Region,Hohhot 010017,China;Department of Anesthesiology,Second Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010020,China)

机构地区：[1]内蒙古医科大学药学院,内蒙古呼和浩特010110 [2]内蒙古自治区人民医院内镜中心,内蒙古呼和浩特010017 [3]内蒙古医科大学第二附属医院麻醉科,内蒙古呼和浩特010020

出　　处：《药物生物技术》2022年第6期551-556,共6页Pharmaceutical Biotechnology

基　　金：高校青年科技英才(No.NJYT22007)。

摘　　要：以二硬脂酰磷脂酰乙醇胺-聚乙二醇(DSEP-PEG2000)为载体材料,包载槲皮素,制备两亲性聚合物胶束纳米给药系统,并评价其对乳腺癌MCF-7细胞的体外抗肿瘤效果。采用薄膜水化法制备负载槲皮素的聚合物胶束(Qu@DSPE-PEG),通过透射电子显微镜观察其微观形貌,粒度仪测定其粒径分布及Zeta电位,采用透析袋考察体外释药特性;评价Qu@DSPE-PEG聚合物胶束的安全性;并对乳腺癌MCF-7细胞的生长抑制及凋亡情况进行考察。制备的Qu@DSPE-PEG聚合物胶束外观呈球形,粒度分布较为均匀,粒径为(13.91±2.14) nm,多分散系数(PDI)为0.169±0.062,Zeta电位为(-10.31±4.81) mV,包封率为95.06%,载药量为3.10%;24 h时,Qu@DSPE-PEG聚合物胶束累积释放34.19%,并对人乳腺癌细胞MCF-7的抑制作用显著高于槲皮素游离药物,且能显著促进人乳腺癌细胞MCF-7的凋亡。本研究制备的Qu@DSPE-PEG聚合物胶束对乳腺癌MCF-7细胞抑制更显著,具有潜在的临床应用价值,值得进一步研究。Absrtact Taking amphiphilic block copolymers material distearyl phosphatidyl ethanolamine-polyethylene glycol(DSEP-PEG2000) as the carrier material and the insoluble quercetin is loaded, and the amphiphilic polymer micellar nano-delivery system is prepared, that is, the quercetin polymer micelles, and studies the biological effect and in vivo safety of the quercetin polymer micelles by evaluating its in vitro anti-tumor effect on MCF-7 cells of breast cancer.The quercetin polymer micelles(Qu@DSPE-PEG) were prepared by thin-film hydration methodology, establishing ultraviolet spectrophotometry for methodological investigation of quercetin polymer micelles, which the microscopic morphology was observed by transmission electron microscopy.The particle size distribution and Zeta potential were determined by laser particle size analyzer and the in vitro release characteristics were investigated by dialysis method.The safety of the quercetin polymer micelles(Qu@DSPE-PEG) were evaluated by hemolytic experiments.The antitumor effect of the quercetin polymer micelles(Qu@DSPE-PEG) were studied through growth inhibition and apoptosis of MCF-7 cells in breast cancer.The quercetin polymer micelles(Qu@DSPE-PEG) has a spherical appearance with a relatively uniform particle size distribution of(13.91±2.14) nm, a polydispersion coefficient(PDI) of 0.169±0.062,and a Zeta potential of(-10.31±4.81) mV.The content determination by ultraviolet spectrophotometry illustrated that the encapsulation rate of the quercetin polymer micelles(Qu@DSPE-PEG) are 95.06% and the drug loading is 3.10%.In vitro drug release experiments showed that at 24 h, the cumulative release of the quercetin polymer micelles(Qu@DSPE-PEG) only reached 34.19%.Cytotoxicity tests and apoptosis experiments illustrated that the inhibition effect of the quercetin polymer micelles(Qu@DSPE-PEG) on human breast cancer cells MCF-7 was significantly higher than that of free quercetin, and could significantly promote the apoptosis of human breast cancer cells MCF-7.The Qu@

关 键 词：槲皮素 纳米给药系统 生物学效应 抗肿瘤 细胞毒性 细胞凋亡 

分 类 号：R284[医药卫生—中药学] R944[医药卫生—中医学]