| 引用本文： |
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张旭南,王培军.靶向整合素αvβ3受体磁共振/荧光双模态成像纳米探针的体外成像性能及光动力治疗效应评价[J].同济大学学报（医学版）,2018,39(2):32-37. [点击复制]
- ZHANG Xu-nan,WANG Pei-jun.Magnetic resonance imaging and photodynamic therapeutic effects in vitro of nanoprobe RGD-Gd@BSA-Ce6 targeting αvβ3 receptor[J].同济大学学报（医学版）,2018,39(2):32-37. [点击复制]
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| 摘要: |
| 目的探讨RGD-Gd@BSA-Ce6纳米探针对A549肺癌细胞的磁共振/荧光显像效果和光动力治疗作用。方法构建靶向和非靶向纳米探针RGD-Gd@BSA-Ce6和Gd@BSA-Ce6。采用体外磁场发生仪和3.0T临床医用磁共振仪采集RGD-Gd@BSA-Ce6和商品化Gd-DTPA的T1弛豫时间和T1加权图像。通过激光共聚焦显微镜观察光敏剂二氢卟啉e6(chlorin e6，Ce6)、Gd@BSA-Ce6及RGD-Gd@BSA-Ce6纳米探针与A549肺癌细胞的结合能力效果。通过细胞增殖-毒性检测（CCK8试剂盒法)评估3种药物对肿瘤的光动力治疗效果。通过细胞增殖-毒性检测（MTT试剂盒法）评估3种药物对293T细胞（人胚胎肾细胞）的生物安全性。结果RGD-Gd@BSA-Ce6较Gd-DTPA具有更高的T1弛豫率，其T1弛豫系数为18.615。同时，RGD-Gd@BSA-Ce6的T1加权图信号显著高于Gd-DTPA。激光共聚焦成像结果表明，RGD-Gd@BSA-Ce6和Gd@BSA-Ce6对A549细胞的结合能力均高于光敏剂Ce6；同时，RGD-Gd@BSA-Ce6对A549细胞的结合能力明显高于Gd@BSA-Ce6。细胞光动力治疗结果证实，两种纳米探针处理组的细胞存活率都低于光敏剂Ce6处理组（P<0.05)，同时RGD-Gd@BSA-Ce6组的细胞存活率明显低于Gd@BSA-Ce6组（P<0.05）。细胞水平的生物安全性实验表明，不同药物浓度下，293T细胞的存活率并未发生明显改变，且各组存活率均高于60%。结论RGD-Gd@BSA-Ce6比商品化Gd-DTPA具有更高T1弛豫性能；体外实验证实RGD-Gd@BSA-Ce6纳米探针对A549肺癌细胞具有显著的结合能力；光动力治疗实验具有明显的杀伤A549肿瘤细胞的作用；MTT实验表明RGD-Gd@BSA-Ce6纳米探针具有良好的生物安全性。 |
| 关键词: 肺肿瘤 整合素αvβ3受体 精氨酸-甘氨酸-天冬氨酸 磁共振/荧光成像 光动力治疗 |
| DOI：10.16118/j.1008-0392.2018.02.007 |
| 投稿时间：2018-01-08 |
| 基金项目:国家自然科学基金（81571655） |
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| Magnetic resonance imaging and photodynamic therapeutic effects in vitro of nanoprobe RGD-Gd@BSA-Ce6 targeting αvβ3 receptor |
| ZHANG Xu-nan,WANG Pei-jun |
| (Dept. of Radiology, Tongji Hospital, Tongji University, Shanghai 200065, China) |
| Abstract: |
| ObjectiveTo evaluate the imaging and photodynamic therapy treatment (PDT) efficacy of nanoprobe RGD-Gd@BSA-Ce6 on non-small cell lung cancer（NSCLC）A549 cells.MethodsThe protein nanoprobe RGD-Gd@BSA-Ce6 and Gd@BSA-Ce6 were synthesized. The T1 relaxation time of RGD-Gd@BSA-Ce6 and Gd-DTPA was collected by in vitro magnetic field generator and both T1-weighted images were attained by using 3.0T magnetic resonance scanner. The affinity of the chlorine6（Ce6）, Gd@BSA-Ce6 and RGD-Gd@BSA-Ce6 with A549 cells was observed by laser confocal fluorescence imaging, the PDT effect was determined by CCK-8 assay (cell counting Kit-8). The biosecurity of three drugs to human embryonic kidney 293T cells was assessed by MTT assay. ResultsRGD-Gd@BSA-Ce6 showing relaxation coefficient 18.615 had higher T1relaxation rate and T1-weighted enhanced imaging signal compared with Gd-DTPA. More distinct property of affinity with A549 cells was observed in group RGD-Gd@BSA-Ce6 and group Gd@BSA-Ce6 by laser confocal fluorescence imaging, both were better than free Ce6, and RGD-Gd@BSA-Ce6 showed higher affinity with A549 cells than Gd@BSA-Ce6. PDT tests showed that relative cell viability in RGD-Gd@BSA-Ce6 and Gd@BSA-Ce6 groups were significantly lower than that in Ce6 group (P<0.05) ; while the cell viability in RGD-Gd@BSA-Ce6 group was lower than that in Gd@BSA-Ce6 group（P<0.05）. The biosecurity assay in vitro showed that there were no significant changes in 293T cells under different drug concentrations, and relative cell viability was all higher than 60%. ConclusionRGD-Gd@BSA-Ce6 has a better T1 relaxation performance than commercial Gd-DTPA. In vitro experiments proves that RGD-Gd@BSA-Ce6 protein nanoprobe has a high affinity with A549 cell and significant PDT effect on A549 cell with a good biosecurity. |
| Key words: lung cancer integrin receptor arginine-glycine-aspartate MRI/Fluorescence imaging photodynamic therapy treatment |
