贵州医科大学学报

2016, v.41;No.192(09) 1047-1052+1060

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pH敏感磁靶向纳米给药系统的构建及其对HepG2肿瘤细胞的作用
Construction of A pH-sensitive Magnetic Targeting Nano-drug Delivery System and Its Effect on HepG2 Tumor Cells

马红岩;乔桂红;
MA Hongyan;QIAO Guihong;Department of Clinical Medicine,Shangqiu Medical College;

摘要(Abstract):

目的:构建一种新型的磁性靶向p H敏感控释纳米给药系统并考察其对Hep G2肿瘤细胞的抑制作用。方法:将四氧化三铁(Fe3O4)衍生至碳纳米管(CNTs)表面,使用聚乙烯亚胺/聚乙二醇对载体进行修饰,利用聚乙烯亚胺具有的丰富的氨基末端与阿霉素(DOX)结合,通过具有p H敏感的腙键相连构建CNTs-Fe3O4-PEI/PEG-DOX给药系统;分别使用透射电镜(TEM)、X射线衍射仪(XRD)、傅里叶红外光谱仪(FT-IR)、磁强计(VSM)对给药系统进行相关表征分析,考察给药系统热疗升温、载药及p H敏感释放情况;将培养的Hep G2肿瘤细胞分为空白对照组、CNTs-Fe3O4-PEI/PEG组、PTT热疗组、DOX组、DOX联合PTT热疗组、CNTs-Fe3O4-PEI/PEG-DOX组、CNTs-Fe3O4-PEI/PEG-DOX联合PTT热疗组、CNTs-Fe3O4-PEI/PEG-DOX磁性靶向联合PTT热疗处理组,使用MTT法检测以上8组中Hep G2细胞的抑制率。结果:成功构建CNTs-Fe3O4-PEI/PEG-DOX纳米给药系统,DOX的载药率为65.04%,p H值降低时,DOX的累计释放率明显迅速升高;该给药系统的磁化强度为19.92 emu/g,具有明显的磁性靶向性;CNTs-Fe3O4-PEI/PEG-DOX在近红外光照射下可在5 min内迅速升温至(58.7±2.5)℃,具有明显的热疗升温作用;给药系统联合热疗对肿瘤细胞具有明显的抑制作用。结论:CNTsFe3O4-PEI/PEG-DOX是一种新型的具有磁性靶向、p H敏感控释以及热疗作用的多功能智能化的给药系统,对Hep G2肿瘤细胞有较强的抑制率。
Objective: To construct a new type of magnetic-targeting and p H-sensitive controlled release drug delivery system and investigate its inhibitory effect on Hep G2 tumor cells. Method: Fe3O4 nanoparticles were loaded onto the surface of carbon nanotubes( CNTs). Then,polyethyleneimine( PEI) and poly( ethylene glycol)( PEG) were used to functionalized the carrier. Finally,doxorubicin( DOX) was conjugated to the amino groups of PEI through p H-sensitive hydrazone bonds to construct the CNTs-Fe3O4-PEI / PEG-DOX drug delivery system. Transmission electron microscope( TEM),X-ray diffractometer( XRD),fourier transform infrared spectrometer( FT-IR) and magnetometer were adopted to analyze the characteristics of this drug delivery system. The hyperthermia effect,drug loading rate and p H-sensitive controlled release in vitro were investigated. The Hep G2 tumor cells were divided into control group,CNTs-Fe3O4-PEI / PEG group,PTT hyperthermia group,DOX group,DOX PTT combined with hyperthermia group,CNTs-Fe3O4-PEI / PEG-DOX group,CNTs-Fe3O4-PEI / PEG-DOX combined with PTT hyperthermia group,and CNTs-Fe3O4-PEI / PEG-DOX magnetic targeting combined with PTT hyperthermia group,and MTT method was used to detect the inhibitory rates of Hep G2. Results: The CNTs-Fe3O4-PEI / PEG-DOX drug delivery system was constructed successfully,and DOX loading rate was 65. 04%( WDOX: WCNTs-Fe3O4-PEI / PEG). When the p H value was decreased,the cumulative release rate of DOX was increased significantly,which proved that the drug delivery system had p H sensitive controlled release properties. The magnetic investigation results showed that the magnetization of the drug delivery system was 19. 92 emu / g,showing obvious magnetic targeting. The drug delivery system can rapidly heated up to( 58. 7 ± 2. 5) ℃ in 5 minutes with the near infrared light treated,showing obvious hyperthermia warming effect. The combination of chemotherapy and photothermal therapy had significant inhibitory effects on growth of Hep G2 tumor cells. Conclution: CNTs-Fe3O4-PEI / PEG-DOX is a new type of multifunctional intelligent drug delivery system with magnetic-targeting,p H-sensitive controlled release and hyperthermia effects,which has significant inhibitory effects on growth of Hep G2 tumor cells.

关键词(KeyWords): 磁靶向;碳纳米管;pH敏感;阿霉素;热疗
magnetic targeting;carbon nanotubes;pH-sensitive;doxorubicin;photothermal therapy

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基金项目(Foundation): 商丘市科技发展计划项目(153051)

作者(Author): 马红岩;乔桂红;
MA Hongyan;QIAO Guihong;Department of Clinical Medicine,Shangqiu Medical College;

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