| 郑树,魏启春,沈俐,Erika Bohl Kullberg,Lars Gedda.HER-2靶向硼脂质体的细胞靶向与细胞内分布研究[J].中华放射医学与防护杂志,2005,25(4):312-315 |
| HER-2靶向硼脂质体的细胞靶向与细胞内分布研究 |
| Cellular targeting and subcellular distribution of HER-2 targeting boron liposomes |
| 投稿时间：2005-02-28 |
| DOI： |
| 中文关键词: 硼中子俘获治疗 脂质体 细胞靶向 细胞滞留 |
| 英文关键词:Boron neutron capture therapy Liposome Cellular targeting Cellular retention |
| 基金项目:国家自然科学基金资助项目(30470501) |
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| 摘要点击次数: 2094 |
| 全文下载次数: 1947 |
| 中文摘要: |
| 目的 分析新制备的HER2靶向硼脂质体在细胞靶向、滞留及细胞内分布等方面的特性,探讨该脂质体作为靶向给药系统用于硼中子俘获治疗研究的可能性。方法 分别从靶向剂Trastuzumab、脂质体和装载的WSA3个方面观察SKBR3细胞对125ITrastuzumabWSA3H脂质体的摄取与滞留。Trastuzumab标记了125I用伽玛计数器检测;脂质体标记了3H用液闪计数器检测;WSA用感应耦合等离子体质谱仪检测。激光共聚焦显微镜观察WSA在细胞内的分布。结果 最初8h细胞对125ITrastuzumab的摄取量快速增加,24h后细胞内125I量反而有所下降。细胞对3H脂质体的摄取随培养时间而增加,直到48h也没有达到平台期。培养4、8及24h,细胞含硼量分别达到55、78及132×10-6。细胞摄取125ITrastuzumabWSA3H脂质体后,在普通培养液中培养24和48h,分别有90%、67%的WSA滞留在细胞内。激光共聚焦显微镜下显示大部分WSA位于细胞浆。结论 细胞摄取量满意,WSA在细胞内滞留时间长,说明125ITrastuzumabWSA3H脂质体是一个很好的运载工具,有希望应用于硼中子俘获治疗研究。 |
| 英文摘要: |
| Objective To investigate HER-2 targeting boron liposomes as a potential drug delivery vehicle for boron neutron capture therapy, in respect to cellular uptake, retention and the subcellular location. Methods Cellular uptake and retention of 125I-Trastuzumab-WSA- 3H-Liposomes were studied using SK-BR-3 cells, with regard to the targeting agent, carriers, and the loaded WSA. As there was 125I labeled on Trastuzumab and 3H on liposomes, Trastuzumab and the liposomes could be measured using a gamma counter and a liquid scintillation counter,respectively. WSA could be measured by inductively coupled plasma mass spectrometry (ICP-MS). Subcellular distribution of WAS was studied using confocal microscopy. Results The uptake of 125I labeled Trastuzumab reached a plateau after 8 h and declined after 24 h incubation. For 3H-Liposome, there was a different uptake pattern, i.e., no plateau was reached and no decline was seen even after 48 h incubation. The boron uptake increased with prolongation of incubation time, for 4, 8 and 24 hours′ incubation, it reached 55 ppm, 78 ppm, and 123 ppm, respectively. After incubation in conventional medium for 24 h over 90% WSA and 70% of the 3H-Liposomes still remained in the cells, while only 35% of the 125I-Trastuzumab remained. The difference was even more pronounced after 48 h when 67% WSA and 55% of the 3H-Liposome still remained in the cells as compared to 18% for the 125I-Trastuzumab. WSA was clearly visualized within the cell mainly in the cytoplasm. Conclusion The developed HER-2 targeting boron liposomes could be considered as a potent drug delivery system for boron neutron capture therapy, since it has high cellular boron uptake with a long retention time. |
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