基于类芬顿反应构建磁性纳米粒治疗卵巢癌:体外实验  

Construction of magnetic nanoparticles for treating ovarian cancer based on Fenton like reaction:In vitro experiments

作　　者：周炜程 李锐 张亮[2] 黄菊 ZHOU Weicheng;LI Rui;ZHANG Liang;HUANG Ju(Department of Ultrasound,the Third Affiliated Hospital of Chongqing Medical University,Chongqing 401120,China;Department of Ultrasound,the Second Affiliated Hospital of Chongqing Medical University,Chongqing Key Laboratory of Ultrasound Molecular Imaging,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属第三医院超声科,重庆401120 [2]重庆医科大学附属第二医院超声科,超声分子影像重庆市重点实验室,重庆400010

出　　处：《中国医学影像技术》2021年第6期830-835,共6页Chinese Journal of Medical Imaging Technology

基　　金：重庆医科大学附属第三医院科研孵化项目(KY08025);重庆市英才计划[渝委人才(2019)4号]。

摘　　要：目的构建具有类芬顿反应性能的磁性靶向纳米粒,评价其体外光声成像效果及联合催化反应下抑制卵巢癌细胞的作用。方法以双乳化法制备包裹四氧化三铁(Fe_(3)O_(4))及葡萄糖氧化酶(GOx)的磁性聚乳酸羟基乙酸共聚物(PLGA)纳米粒Fe_(3)O_(4)@PLGA-GOx,观察其基本特性、体外稳定性及释药效果;采用酶标仪监测其联合催化活性,以共聚焦显微镜观察细胞摄取纳米粒能力;以荧光显微镜和流式细胞术观察纳米粒在联合催化作用下产生细胞毒性活性氧的能力;用细胞计数试剂盒(CCK-8)检测磁性Fe_(3)O_(4)@PLGA-GOx体外杀伤人卵巢癌SKOV3细胞的能力,并评价其体外光声成像效果。结果成功制备出磁性纳米粒Fe_(3)O_(4)@PLGA-GOx,平均粒径(290.81±108.52)nm,表面电位(-18.41±5.90)mV;Fe_(3)O_(4)及GOx的包封率分别为(91.34±2.35)%和(26.53±6.72)%。外部磁场作用下,细胞对纳米粒摄取增加;随纳米粒浓度增加,光声信号增强。Fe_(3)O_(4)@PLGA-GOx可介导类芬顿反应,产生活性氧并发挥细胞毒性作用杀伤肿瘤细胞。结论成功制备的具有类芬顿反应性能磁性纳米粒在光声成像引导下具有体外催化治疗肿瘤细胞作用。Objective To prepare magnetic-targeting nanoparticles with Fenton-like reaction performance,and to evaluate their capability in photoacoustic imaging and inhibitory effect on ovarian cancer cells induced by synergetic catalysis.Methods Magnetic poly(lactic-co-glycolic acid)(PLGA)nanoparticle encapsulating Fe_(3)O_(4)and glucose oxidase(GOx)(Fe_(3)O_(4)@PLGA-GOx)were prepared using double emulsion.The basic characteristics,stability and in vitro release of magnetic nanoparticles were detected.The catalytic activity of Fe_(3)O_(4)@PLGA-GOx was monitored with microplate instrument,the uptake efficiency of cells was observed using confocal laser scanning microscopy,and the active oxygen generation of nanoparticles was evaluated with fluorescence microscope and flow cytometry.The killing ability of magnetic Fe_(3)O_(4)@PLGA-GOx on human ovarian cancer SKOV3 cells was analyzed with cell counting kit-8(CCK-8),and the in vitro photoacoustic imaging performances were evaluated.Results The magnetic nanoparticles were successfully prepared,with an average size around(290.81±108.52)nm and surface zeta potential at(-18.41±5.90)mV.The encapsulation efficiency of Fe_(3)O_(4)and GOx in Fe_(3)O_(4)@PLGA-GOx nanoparticles was(91.34±2.35)%and(26.53±6.72)%,respectively,which enhanced under external magnetic field.The photoacoustic signals increased with Fe_(3)O_(4)@PLGA-GOx concentration.With Fenton-like reaction induced by Fe_(3)O_(4)@PLGA-GOx,active oxygen was produced to exert killing effect on tumor cells.Conclusion Magnetic-targeting nanoparticles with Fenton-like reaction performance were successfully fabricated,which could induce catalytic effect on tumor cells in vitro under the guidance of photoacoustic imaging.

关 键 词：卵巢肿瘤 磁性纳米粒 类芬顿反应 光声成像 

分 类 号：R737.31[医药卫生—肿瘤]