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八臂聚乙二醇纳米结合物脑靶向传递光疗剂的研究

辛俊勃, 李芳, 李若菡, 张冉, 潘富荣, 明欣

辛俊勃, 李芳, 李若菡, 张冉, 潘富荣, 明欣. 八臂聚乙二醇纳米结合物脑靶向传递光疗剂的研究[J]. 中国药科大学学报, 2019, 50(3): 299-307. DOI: 10.11665/j.issn.1000-5048.20190305
引用本文: 辛俊勃, 李芳, 李若菡, 张冉, 潘富荣, 明欣. 八臂聚乙二醇纳米结合物脑靶向传递光疗剂的研究[J]. 中国药科大学学报, 2019, 50(3): 299-307. DOI: 10.11665/j.issn.1000-5048.20190305
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XIN Junbo, LI Fang, LI Ruohan, ZHANG Ran, PAN Furong, MING Xin. Eight-arm polyethylene glycol nanoconjugates for brain targeted delivery of photosensitizer[J]. Journal of China Pharmaceutical University, 2019, 50(3): 299-307. DOI: 10.11665/j.issn.1000-5048.20190305
Citation: XIN Junbo, LI Fang, LI Ruohan, ZHANG Ran, PAN Furong, MING Xin. Eight-arm polyethylene glycol nanoconjugates for brain targeted delivery of photosensitizer[J]. Journal of China Pharmaceutical University, 2019, 50(3): 299-307. DOI: 10.11665/j.issn.1000-5048.20190305
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八臂聚乙二醇纳米结合物脑靶向传递光疗剂的研究

  • 1.

    江苏医药职业学院药学院

  • 2.

    维克森林大学医学院肿瘤生物学部

基金项目: 江苏省自然科学基金资助项目(No.BK20180273)；江苏省青蓝工程资助项目(2019)；江苏医药职业学院科技创新团队资助项目(No.20188103)；江苏省大学生创新创业训练计划资助项目(No.201912682017Y)

Eight-arm polyethylene glycol nanoconjugates for brain targeted delivery of photosensitizer

摘要

    摘要
  • 摘要: 以八臂聚乙二醇为载体、cRGD为靶头制备用于脑癌靶向光疗的纳米结合物，探讨其抗肿瘤作用与机制。通过紫外可见光谱对合成的纳米结合物进行表征，借助激光共聚焦显微镜对纳米结合物的细胞摄取行为进行观察，采用Alamar Blue法与Calcein AM/PI染色考察细胞毒作用，借助肿瘤球生长曲线评估肿瘤抑制效果，通过观察细胞内活性氧的生成、细胞凋亡与肿瘤球穿透性探讨纳米结合物的作用机制。结果表明，cRGD-8PEG-IR700能够被整合素受体高表达的U87MG细胞高效摄取，而整合素受体不表达的NIH/3T3细胞对其几乎无摄取。在考察浓度范围内，仅cRGD-8PEG-IR700光照组的U87MG细胞呈现明显毒性作用；在3D细胞模型上仅cRGD-8PEG-IR700光照组的肿瘤球生长受到明显抑制，这是由于光照诱导细胞内活性氧的产生并引起细胞凋亡和靶向纳米结合物较强的肿瘤穿透性能。因此，该聚乙二醇纳米结合物具有肿瘤靶向性，有望为肿瘤的光疗提供一个有前景的药物递送系统。
    Abstract: The aim of this study was to prepare the nanoconjugates for targeted photodynamic therapy of brain cancer by using eight-arm polyethylene glycol(8PEG)as the carrier and cRGD as the targeting ligand, and to investigate the antitumor effect and its mechanism. UV-Vis spectra and confocal microscopy were used for characterization and cellular uptake behavior of nanoconjugates respectively. Alamar Blue assay and Calcein AM/PI staining were applied to investigate the cytotoxocity of nanoconjugates against tumor cells, and tumor spheroid growth curve was used to assess the tumor growth suppression effect. In addition, the generation of reactive oxygen species(ROS), apoptosis and spheroid permeability test was used to reveal the antitumor mechanism of nanoconjugates. The results showed that cRGD-8PEG-IR700 was taken up efficiently by integrin overexpressed U87MG cells, while almost no uptake was found in integrin free NIH/3T3 cells. Remarkable photokilling effect against U87MG cells was only shown in cRGD-8PEG-IR700 group due to the light-induced ROS generation and apoptosis, whereas growth suppression effect was also observed in U87MG spheroids treated with cRGD-8PEG-IR700 plus light owing to the superior penetration ability of targeted nanoconjugates. Hence, tumor-targeted PEG nanoconjugates may provide a promising drug delivery system for photodynamic therapy of cancers.
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  • 刊出日期:  2019-06-24

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