pH响应性磁性介孔纳米载药系统的制备

doi:10.16085/j.issn.1000-6613.2022-2032

摘要/Abstract

摘要：

研究开发了一种基于磁性介孔二氧化硅和聚多巴胺（PDA）混合体的智能给药平台，可用于pH响应性给药。通过共沉淀法制备Fe₃O₄，以十六烷基三甲基溴化铵（CTAB）为模板，硅酸四乙酯（TEOS）为硅源，通过Stober法获得了磁性纳米材料Fe₃O₄@mSiO₂。负载抗癌药物阿霉素（DOX）后，通过碱性条件下多巴胺的氧化自聚合，在其表面形成pH敏感的PDA涂层，得到DOX/Fe₃O₄@mSiO₂@PDA磁性纳米载药系统。通过透射电子显微镜、X射线衍射、傅里叶红外光谱仪、比表面积测试和振动样品磁强计等技术手段对材料进行表征。结果表明Fe₃O₄@mSiO₂的形貌为球形，拥有良好介孔结构和高达619.16m²/g的比表面积；VSM表明载体Fe₃O₄@mSiO₂@PDA具有良好的磁性。当载药过程中DOX浓度为0.5mg/mL、温度为37℃，反应36h后，载药率为51.69%，包封率为82.70%。释药曲线表明纳米载药系统具有pH响应性和药物缓释的特点；噻唑蓝比色法（MTT法）细胞毒性实验表明Fe₃O₄@mSiO₂@PDA生物相容性良好，DOX/Fe₃O₄@mSiO₂@PDA有良好的抗肿瘤效果。该纳米载药系统在药物靶向递送中具有潜在的应用前景。

关键词: 四氧化三铁, 磁性纳米材料, 介孔, pH响应性, 药物递送, 阿霉素

Abstract:

We developed an intelligent drug delivery platform based on the mixture of magnetic mesoporous silica and polydopamine (PDA), which can be used for pH responsive drug delivery. Magnetic cores Fe₃O₄ was prepared by co-precipitation method. The magnetic nanomaterial Fe₃O₄@mSiO₂ was obtained by the Stober method using cetyltrimethylammonium bromide (CTAB) as a template and tetraethyl silicate (TEOS) as a silicon source. Anticancer drug doxorubicin (DOX) was used as the model drug to be encapsulated into Fe₃O₄@mSiO₂. The surface of the carrier was modified with pH-sensitive PDA coating by oxidation self-polymerization of dopamine at alkaline pH to obtain the magnetic nano drug loading system DOX/Fe₃O₄@mSiO₂@PDA. The materials were characterized by Transmission electron microscope, X-ray diffraction, Fourier Transform infrared spectrometer, Brunauer Emmett Teller and vibration sample magnetometer. We found that Fe₃O₄@mSiO₂ was spherical with good mesoporous structure and a specific surface area of up to 619.16m²/g. VSM indicated that the carrier Fe₃O₄@mSiO₂@PDA had good magnetic properties. During the drug loading process, when DOX concentration was 0.5mg/mL, temperature was 37℃, and reaction time was 36h, the drug loading rate and encapsulation rate were up to 51.69% and 82.70%, respectively. The drug release curve showed that the nano drug delivery system had the characteristics of pH responsiveness and slow drug release. Thiazole blue colorimetric assay (MTT) cytotoxicity showed that Fe₃O₄@mSiO₂@PDA had good biocompatibility, and DOX/Fe₃O₄@mSiO₂@PDA had obvious inhibitory effect on cancer cells. The nano drug delivery system has a potential application prospect in targeted drug delivery.

Key words: ferric oxide, magnetic nanomaterials, mesoporous, pH responsiveness, drug delivery, doxorubicin (DOX)

中图分类号:

O614.881

刘慧慧, 史笑飞, 王倩男, 刘锦博, 张静. pH响应性磁性介孔纳米载药系统的制备[J]. 化工进展, 2023, 42(10): 5390-5398.

LIU Huihui, SHI Xiaofei, WANG Qiannan, LIU Jinbo, ZHANG Jing. Preparation of pH responsive magnetic mesoporous nanoparticle drug loading system[J]. Chemical Industry and Engineering Progress, 2023, 42(10): 5390-5398.

图/表 15

图1 DOX/Fe3O4@mSiO2@PDA制备流程示意图

图2 DOX溶液的紫外全波长扫描曲线(a)和标准曲线(b)

图3 多巴胺的氧化聚合反应

图4 Fe3O4和Fe3O4@mSiO2的XRD图谱

图5 Fe3O4@mSiO2、DOX/Fe3O4@mSiO2@PDA的N2吸附-脱附曲线

图6 Fe3O4@mSiO2、DOX/Fe3O4@mSiO2@PDA的BJH孔径分布曲线

图7 Fe3O4、Fe3O4@mSiO2和Fe3O4@mSiO2@PDA的FTIR图

图8 Fe3O4 (a)、Fe3O4@mSiO2 (b)的TEM图

图9 Fe3O4 (a)、Fe3O4@mSiO2 (b)的粒径分布图

图10 Fe3O4、Fe3O4@mSiO2和Fe3O4@mSiO2@PDA的磁滞回线图（1Oe=79.58A/m）

图11 DOX浓度与载药率、包封率的关系

图12 时间与载药率、包封率的关系

图13 温度与载药率、包封率的关系

图14 DOX/Fe3O4@mSiO2@PDA的药物释放曲线

图15 Hela细胞和Fe3O4@mSiO2@PDA、DOX/Fe3O4@mSiO2@ PDA与DOX作用24h后的相对活力大小

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