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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。
OBJECTIVE: To analyze the characteristics of targeting, retention and intracellular distribution of newly prepared HER2 targeting liposomes in vitro, and to explore the possibility of using this liposome as targeted delivery system for boron neutron capture therapy. Methods The uptake and retention of 125Trastuzumab WSA3H liposomes by SKBR3 cells were observed respectively from Targeting agents Trastuzumab, liposomes and loaded WSA3. Trastuzumab labeled 125I with a gamma counter; liposome labeled 3H with a liquid scintillation counter; WSA with an inductively coupled plasma mass spectrometer. Laser confocal microscopy was used to observe the distribution of WSA in the cells. Results The uptake of 125ITrastuzumab in the first 8h cells increased rapidly, but the amount of 125I decreased after 24h. Uptake of 3H liposomes by the cells increased with incubation time and did not reach the plateau until 48 h. After cultured for 4, 8 and 24 h, the content of boron in cells reached 55, 78 and 132 × 10-6, respectively. Cells were inoculated with 125ITrastuzumabWSA3H liposomes and cultured in normal medium for 24 and 48 hours, respectively, with 90% and 67% of WSA residing in the cells. Confocal laser scanning microscopy showed most of the WSA was located in the cytoplasm. Conclusions The cell uptake is satisfactory and WSA remains in the cell for a long time, which indicates that 125ITrastuzumab WSA3H liposome is a good carrier and promising for boron neutron capture therapy.