癌细胞膜伪装的纳米递药系统的初步构建与评价  

Construction and evaluation of a nano-drug delivery system camouflaged by cancer cell membrane

作　　者：杨洪宾 余真妍 闫洁 纪帅帅 杨梦婷 胡嫚 王子吟 霍强 程秀 YANG Hongbin;YU Zhenyan;YAN Jie;JI Shuaishuai;YANG Mengting;HU Man;WANG Ziyin;HUO Qiang;CHENG Xiu(Department of Medicinal Chemistry,School of Pharmacy,Bengbu Medical College,Bengbu 233000,China)

机构地区：[1]蚌埠医学院药学院药物化学教研室,蚌埠233000

出　　处：《山西医科大学学报》2022年第2期127-133,共7页Journal of Shanxi Medical University

基　　金：安徽省教育厅重大项目(KJ2020ZD52);安徽省自然科学基金项目(1908085MH292)。

摘　　要：目的制备肺癌细胞膜(lung cancer cell membrane,CM)包裹的仿生纳米靶向载体,并对其进行评价。方法通过一锅包封法将槲皮素(quercetin,QT)载入沸石咪唑骨架(zeolitic imidazolate framework-8,ZIF-8),得到纳米药物(zeolitic imidazolate framework-8@quercetin,ZIF-8@QT)。将A549细胞膜与二硬脂酰基乙醇胺(distearoyl phosphoethanolamine,DSPE)混合,并与ZIF-8@QT通过水浴超声法包裹到纳米药物上,完成仿生纳药物(lung cancer cell membrane-distearoyl phosphoethanolamine-zeolitic imidazolate framework-8@quercetin,CMD-ZIF-8@QT)的构建。对CMD-ZIF-8@QT的粒径、形貌、稳定性、封装效率、体外释药性进行评价,并进行体内分布与药效实验。结果表征实验结果显示CMD-ZIF-8@QT的平均粒径为(176.4±2.72)nm,形状为类球形。制剂学评价表明仿生纳米药物载药量为16.8%±0.64%,包封率为84.2%±1.42%,且具有良好的酸敏感性和稳定性。体内分布实验结果表明,与Cy5组相比,Cy5-CMD-ZIF-8组仿生纳米载体在体内富集到肿瘤部位(P<0.01)。体内药效实验结果表明,与QT相比,载QT的仿生载体在体内具有更突出的治疗效果(P<0.01)。结论本研究成功制备了一种仿生纳米药物,提高了药物对肿瘤的靶向性与治疗效果,降低了槲皮素的副作用,提高了用药安全性。Objective To prepare and evaluate a biomimetic nano-targeting carrier wrapped by lung cancer cell membrane(CM).Methods The quercetin(QT)was loaded into the zeolitic imidazolate framework-8(ZIF-8)by one-pot encapsulation method to obtain nano-drug [e-mail] A549 cell membrane was mixed with distearoylethanolamine,and then wrapped with ZIF-8@QT on the nano-drug by water bath ultrasonic method to construct the biomimetic nano-drug.The particle size,the morphology,the stability,the encapsulation efficiency,and the in vitro drug release of the biomimetic nanocarrier were evaluated,and the in vivo distribution and efficacy experiments were carried out.Results The result of characterization experiment showed that the average particle size of CMD-ZIF-8@QT was(176.4±2.72)nm,and the shape was quasi-spherical.The pharmaceutics evaluation showed that the biomimetic nanomedicine had a drug loading content of 16.8%±0.64%,and a loading efficiency of 84.2%±1.42%,and it had well acid sensitivity and stability.The result of in vivo distribution experiment showed that compared with Cy5 group,the biomimetic nanocarriers were enriched to the tumor cells in Cy5-CMD-ZIF-8 group(P<0.01).The results of in vivo pharmacodynamic experiments showed that the QT-carrying bionic carrier had a more prominent therapeutic effect compared with QT(P<0.01).Conclusion The bionic nano-drug is successfully prepared,which can improve the drug targeting and therapeutic effect on tumors,reduce the side effects of quercetin,and improve the safety of medication.

关 键 词：肺癌 细胞膜 ZIF-8 槲皮素 制剂评价 

分 类 号：R96[医药卫生—药理学]