搭载吉西他滨的SiO_(2)@Fe_(3)O_(4)纳米材料抑制裸鼠胰腺癌移植瘤生长的实验研究  

SiO_(2)@Fe_(3)O_(4) nanomaterials loaded with gemcitabine inhibit the growth of nude mice xenograft of pancreatic cancer:An experimental study

作　　者：全棋 管时伟 林泉 彭明晖 俞海波 QUAN Qi;GUAN Shiwei;LIN Quan;PENG Minghui;YU Haibo(Department of Hepatobiliary and Pancreatic Surgery,Wenzhou Central Hospital/Dingli Clinical College of Wenzhou Medical University,Wenzhou,Zhejiang 325000,China)

机构地区：[1]温州医科大学定理临床学院/温州市中心医院肝胆胰外科,浙江温州325000

出　　处：《肝胆胰外科杂志》2023年第12期747-752,756,共7页Journal of Hepatopancreatobiliary Surgery

基　　金：浙江省医药卫生科技计划项目(2020RC113,2022KY1202)。

摘　　要：目的研究搭载吉西他滨(GEM)的SiO_(2)@Fe_(3)O_(4)纳米材料对胰腺癌的疗效及安全性。方法使用FeCl_(3)、聚乙烯吡咯烷酮(PVP)和乙酸钠制得FeCl_(3)微球后,再与硅酸四乙酯(TEOS)反应获得SiO_(2)@Fe_(3)O_(4)纳米微球,并经透射电镜(TEM)及傅里叶变换红外光谱法(FT-IR)表征其结构。与GEM反应制备得GEM-SiO_(2)@Fe_(3)O_(4)纳米颗粒后,计算其载药率及包封率并进行体外药物释放实验。在胰腺癌移植瘤裸鼠中测试GEM-SiO_(2)@Fe_(3)O_(4)纳米颗粒的抑癌效果、器官损害情况及药代动力学。结果TEM示SiO_(2)@Fe_(3)O_(4)复合纳米颗粒呈球形,粒径220~260 nm。FT-IR示SiO_(2)@Fe_(3)O_(4)复合纳米颗粒制备成功。GEM-SiO_(2)@Fe_(3)O_(4)复合纳米颗粒的包封率为84.8%,载药率为7.8%。裸鼠胰腺癌移植瘤实验表明,GEM-SiO_(2)@Fe_(3)O_(4)复合纳米颗粒比游离的GEM抗肿瘤效果更好,并且对正常肝、心、脾、肺、肾组织没有明显损伤。结论本实验研究表明,搭载吉西他滨的SiO_(2)@Fe_(3)O_(4)纳米材料能有效抑制胰腺癌裸鼠移植瘤生长并对正常组织无明显损伤。Objective To investigate the efficacy and safety of SiO_(2)@Fe_(3)O_(4) nanomaterials loaded with gemcitabine(GEM)in the treatmen of pancreatic cancer.Methods FeCl_(3) nanoparticles were synthesized by the reaction of FeCl_(3),polyvinylpyrrolidone(PVP),and sodium acetate.These FeCl_(3) nanoparticles were then reacted with tetraethyl orthosilicate(TEOS)to obtain SiO_(2)@Fe_(3)O_(4) nanoparticles.The structure of the nanoparticles was characterized with transmission electron microscopy(TEM)and Fourier-transform infrared spectroscopy(FTIR).GEM-SiO_(2)@Fe_(3)O_(4) nanoparticles were prepared by reacting GEM with the SiO_(2)@Fe_(3)O_(4) nanoparticles.The drug loading and entrapment efficiency of GEM-SiO_(2)@Fe_(3)O_(4) nanoparticles were calculated.In vitro drug release experiments were conducted to study the release profile of GEM from the nanoparticles.The anticancer effect of GEM-SiO_(2)@Fe_(3)O_(4) nanoparticles,organ damage,and pharmacokinetics were evaluated in nude mice xenograft of pancreatic cancer.Results TEM analysis revealed that the SiO_(2)@Fe_(3)O_(4) composite nanoparticles exhibited a spherical shape,ranging from 220 to 260 nm.FT-IR confirmed the successful synthesis of SiO_(2)@Fe_(3)O_(4) composite nanoparticles.The encapsulation efficiency of GEM-SiO_(2)@Fe_(3)O_(4) nanoparticles was determined to be 84.8%,with a drug loading of 7.8%.Experiments on nude mice xenograft of pancreatic cancer demonstrated that GEM-SiO_(2)@Fe_(3)O_(4) composite nanoparticles exhibited superior anti-tumor effects than that of free GEM.Furthermore,these nanoparticles did not cause significant damage to normal liver,heart,spleen,lungs,or kidney tissues.Conclusion This experimental study shows that SiO_(2)@Fe_(3)O_(4) nanomaterials loaded with GEM effectively inhibit the growth of nude mice xenograft of pancreatic cancer,without significant damage in normal tissues.

关 键 词：胰腺癌 吉西他滨 磁性纳米复合材料 裸鼠 实验研究 

分 类 号：R735.9[医药卫生—肿瘤] R730.53[医药卫生—临床医学]