中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (6): 883-888.doi: 10.3969/j.issn.2095-4344.0063

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

介孔二氧化硅纳米颗粒结合神经干细胞构成靶向光敏药物运输载体用于肿瘤治疗

张卫佳1, 陈家树2
  

  1. 1中山大学新华学院，广东省广州市  523145；2中山大学药学院，广东省广州市  510006
  • 收稿日期:2017-09-08 出版日期:2018-02-28 发布日期:2018-02-28
  • 通讯作者: 陈家树，教授，中山大学药学院，广东省广州市 510006
  • 作者简介:张卫佳，男，1980年生，安徽省安庆市人，汉族，讲师，主要从事现代药物分析研究。

A targeting photodynamic drug vehicle composed of neural stem cells and mesoporous silica nanoparticles for tumor therapy

Zhang Wei-jia1, Chen Jia-shu2
  

  1. 1Xinhua College of Sun Yat-sen University, Guangzhou 523145, Guangdong Province, China; 2Pharmacy School of Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
  • Received:2017-09-08 Online:2018-02-28 Published:2018-02-28
  • Contact: Chen Jia-shu, Professor, Pharmacy School of Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
  • About author:Zhang Wei-jia, Lecturer, Xinhua College of Sun Yat-sen University, Guangzhou 523145, Guangdong Province, China

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文题释义：
介孔二氧化硅颗粒：具有特有的结构特征，相对于其他纳米颗粒有其独特的优势，合成简便，性质稳定，不良反应小，比表面积大，而且可根据不同需求制造出不同种类的二氧化硅纳米颗粒；另外，容易表面修饰，以适应不同的应用需求，例如将壳聚糖修饰在颗粒表面，研发出pH调控缓释载体。
 
背景：神经干细胞对肿瘤细胞没有显著促生长作用，并且其可突破血脑屏障将药物运送到颅内肿瘤组织，目前神经干细胞被大量用于肿瘤药物靶向运输载体研究。
目的：利用介孔二氧化硅纳米颗粒结合神经干细胞形成一个杂合的药物运输载体，探讨该载体是否能够用于光能药物靶向运输。
方法：将光敏药物-酞菁锌包裹于介孔二氧化硅纳米颗粒中。①细胞吞噬实验：采用含不同质量浓度(0，10，50，100，200 mg/L)载酞菁锌介孔二氧化硅纳米颗粒培养液培养神经干细胞6 h，采用荧光显微镜观察细胞内颗粒；②细胞毒性实验：采用含不同质量浓度(0，10，50，100，200 mg/L)载酞菁锌介孔二氧化硅纳米颗粒(或单纯介孔二氧化硅纳米颗粒)培养液分别培养神经干细胞6 h，再常规培养3 d，MTT法检测细胞增殖；③纳米粒子细胞内滞留时间实验：采用含100 mg/L介孔二氧化硅纳米颗粒的培养液培养神经干细胞6 h，再常规培养12，24，72 h，利用荧光显微镜观察细胞内颗粒；④体外激发细胞内药物实验：采用含100 mg/L载酞菁锌介孔二氧化硅纳米颗粒(或单纯介孔二氧化硅纳米颗粒)培养液培养神经干细胞6 h，再常规培养  12 h，以激光照射细胞，利用显微镜观察照射前后的细胞形态；⑤肿瘤细胞杀伤实验：采用含100 mg/L载酞菁锌介孔二氧化硅纳米颗粒培养液培养神经干细胞，再加入乳腺癌细胞MCF7共培养12 h，以激光照射细胞后继续培养12 h，通过荧光显微镜观察细胞死亡情况。
结果与结论：①神经干细胞胞质中有纳米粒子存在，并且随着纳米粒子质量浓度的增加，细胞吞噬的纳米粒子量也增加；②对于有或没有包裹酞菁锌的纳米颗粒，在质量浓度小于100 mg/L时，对神经干细胞活性无明显影响；③培养72 h后，仍然有相当数量的纳米粒子聚集在细胞内；④载酞菁锌介孔二氧化硅纳米颗粒培养的细胞，激光照射后细胞膜发生明显破损；⑤载酞菁锌介孔二氧化硅纳米颗粒培养的神经干细胞与乳腺癌细胞MCF7大量死亡；⑥结果表明，介孔二氧化硅纳米颗粒结合神经干细胞形成的药物运输载体，可用于定点杀死肿瘤细胞。

关键词: 介孔二氧化硅, 神经干细胞, 酞菁锌, 光能治疗, 肿瘤, 生物材料

Abstract:

BACKGROUND: Neural stem cells (NSCs), which exert no promoting effect on tumor growth and break through the blood brain barrier to deliver drugs into tumor tissues, are considered as a promising tumor targeted drug delivery vehicle.
OBJECTIVE: To develop a hybrid delivery system composed of NSCs and moseporous silica nanoparticles for photosensitizer delivery, and to test if the system can be used for tumor therapy.
METHODS: The photosensitizer, zinc phthalocyanine, was encapsulated in mesoporous silica nanoparticles. (1) Cytophagy experiment: NSCs were incubated with mesoporous silica nanoparticles (0, 10, 50, 100, 200 mg/L) loaded with zinc phthalocyanine for 6 hours, and fluorescence microscope was employed to observe the nanoparticles inside the cells. (2) Cytotoxicity test: NSCs incubated with mesoporous silica nanoparticles at various concentrations (0, 10, 50, 100, 200 mg/L) which loaded with or without zinc phthalocyanine for 6 hours, followed by 3 days of normal culture. Then, the cells were harvested for MTT assay. (3) Retention of nanoparticles within the NSCs: 100 mg/L mesoporous silica nanoparticles loaded with zinc phthalocyanine were co-cultured with NSCs for 6 hours. Then, the cells were normally cultured for 12, 24, and 72 hours, and observed with fluorescence microscope. (4) Zinc phthalocyanine excitation in vitro: 100 mg/L mesoporous silica nanoparticles loaded with or without zinc phthalocyanine were co-cultured with NSCs for 6 hours. The cells were then normally cultured for 12 hours and irradiated with laser. Microscope was employed to observe cell morphology. (5)Tumor cell killing experiment: NSCs cells were cultured with 100 mg/L mesoporous silica nanoparticles loaded with zinc phthalocyanine, then mixed with MCF7 cells for 12 hours, and irradiated with laser. After that, the cells were cultured for another 12 hours and cell death was observed under fluorescence microscopy.
RESULTS AND CONCLUSION: (1) After co-cultured with the cells for 6 hours, nanoparticles could be found in the cytoplasm and the number was increased with the concentration of nanoparticles. (2) The nanoparticles with or without zinc phthalocyanine loaded at the concentration of < 100 mg/L showed no toxicity to NSCs. (3) After 72 hours of co-culture, the nanoparticles in the cytoplasm was decreased in number, but still could be found. (4) Laser irradiation could damage the cell membrane of NSCs co-cultured with mesoporous silica nanoparticles loaded with zinc phthalocyanine. (5) A large number of MCF7 cells died after tumor cells were co-cultured with NSCs that were cultured with mesoporous silica. To conclude, the hybrid system composed of NSCs and mesoporous silica nanoparticles loaded with zinc phthalocyanine can serve as a great potential tumor-targeted delivery vehicle for photodynamic therapy. 

Key words: Silicon Dioxide, Neural Stem Cells, Neoplasms, Tissue Engineering

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