基于富勒烯高渗透性磁性纳米递药系统的构建及其磁热性能考察  

High-permeability magnetic nano-drug delivery system based on fullerene and its magnetocaloric properties

作　　者：邓晓兰 王思琴 李馥伶 陈晓亮[1] 侯廷幸 朱文全 DENG Xiao-lan;WANG Si-qin;LI Fu-ling;CHEN Xiao-liang;HOU Ting-xing;ZHU Wen-quan(Department of Pharmacy,Haikou People’s Hospital,Haikou 570208;School of Pharmacy,Qiqihar Medical College,Qiqihar 161006)

机构地区：[1]海口市人民医院药学部,海口570208 [2]齐齐哈尔医学院药学院,齐齐哈尔161006

出　　处：《中南药学》2023年第9期2379-2385,共7页Central South Pharmacy

基　　金：国家自然科学基金项目(No.81873172)。

摘　　要：目的采用一步水热合成法制备C_(60)/Fe_(3)O_(4)-Dox磁性纳米递药系统并考察其磁热性能。方法选择富勒烯(C_(60))作为超顺磁性Fe_(3)O_(4)纳米颗粒的载体,采用一步水热合成法制备C_(60)/Fe_(3)O_(4)纳米载体;通过吸附法装载阿霉素(Dox)构建了C_(60)/Fe_(3)O_(4)-Dox磁性纳米递药系统;采用傅里叶变换红外光谱仪、透射电镜(TEM)和马尔文粒度分析仪等方法对纳米载体进行结构表征;利用红外热成像仪考察不同功率、浓度、质量分数以及介质对C_(60)/Fe_(3)O_(4)-Dox磁性纳米递药系统磁热性能的影响;采用CCK-8法检测不同浓度C_(60)/40%Fe_(3)O_(4)-Dox对4T1细胞活力的影响,通过流式细胞测量术检测细胞凋亡情况。结果表征显示成功制备C_(60)/Fe_(3)O_(4)纳米载体,且载药后粒径由44.61 nm增至61.85 nm,载药量6.21%,包封率74.09%。30 mg·mL-1的C_(60)/40%Fe_(3)O_(4)-Dox分散液在外加磁场(210 V,350 W)作用下于6 min内升温达到42~46℃的目标温度范围。在模拟不同pH的体内环境中,C_(60)/40%Fe_(3)O_(4)-Dox磁性纳米递药系统在肿瘤弱酸性条件下的升温效果优于生理盐水以及弱碱性体液环境。C_(60)/40%Fe_(3)O_(4)对4T1细胞无明显毒性,通过磁热疗作用显著抑制细胞增殖(P<0.05),C_(60)/40%Fe_(3)O_(4)-Dox使细胞凋亡率显著增加(P<0.01)。结论制备的C_(60)/Fe_(3)O_(4)-Dox磁性纳米递药系统在交变磁场中,C_(60)/Fe_(3)O_(4)分散液的升温效果与其浓度、Fe_(3)O_(4)质量分数和磁场功率成正相关;细胞实验证实其具备较好的生物安全性,且在外加磁场作用下,C_(60)/40%Fe_(3)O_(4)-Dox通过磁热疗效应与Dox协同作用可显著诱导4T1细胞凋亡。Objective To prepare C_(60)/Fe_(3)O_(4)-Dox magnetic nano-drug delivery system by one-step hydrothermal synthesis and determine its magnetocaloric properties.Methods Fullerene(C_(60))was selected as the carrier of superparamagnetic Fe_(3)O_(4) nanoparticles,and C_(60)/Fe_(3)O_(4) nanocarriers were prepared by one-step hydrothermal synthesis.C_(60)/Fe_(3)O_(4)-Dox magnetic nanodrug delivery system was constructed by loading doxorubicin(Dox)through adsorption.The structure of nanocarriers was characterized by Fourier transform infrared spectrometer,transmission electron microscope(TEM)and Malvern particle size analyzer.The effect of different power,concentrations,mass fraction and media on the magnetothermal properties of C_(60)/Fe_(3)O_(4)-Dox was determined with an infrared thermographic camera.The effect of different concentrations of C_(60)/40%Fe_(3)O_(4)-Dox on the viability of 4T1 cells was detected by CCK-8 method,and the cell apoptosis was detected by flow cytometry.Results The characterization showed that C_(60)/Fe_(3)O_(4) nanocarriers were successfully prepared,and the particle size after the drug loading increased from 44.61 nm to 61.85 nm,with drug loading of 6.21%.The encapsulation efficiency was 74.09%.C_(60)/40%Fe_(3)O_(4)-Dox dispersion at 30 mg·mL-1 was heated up to the target temperature range of 42~46℃within 6 minutes under the action of an external magnetic field(210 V,350 W).C_(60)/40%Fe_(3)O_(4) had no obvious toxicity to 4T1 cells.The cell proliferation was significantly inhibited by magnetic hyperthermia(P<0.05),and C_(60)/40%Fe_(3)O_(4)-Dox significantly increased the cell apoptosis rate(P<0.01).Conclusion C_(60)/Fe_(3)O_(4)-Dox magnetic nano-drug delivery system has been established.In the alternating magnetic field,the heating effect of C_(60)/Fe_(3)O_(4) dispersion is positively correlated with its concentration,Fe_(3)O_(4) mass fraction and magnetic field power.Cell experiments have confirmed that it is biologically safe,and under the action of an external magnetic field,C_(60)/40%F

关 键 词：富勒烯 Fe_(3)O_(4)纳米颗粒 磁热性能 热疗 

分 类 号：R943[医药卫生—药剂学]