| ZHENG Shu,WEI Qi-chun,SHEN Li,et al.Cellular targeting and subcellular distribution of HER-2 targeting boron liposomes[J].Chinese Journal of Radiological Medicine and Protection,2005,25(4):312-315 |
| Cellular targeting and subcellular distribution of HER-2 targeting boron liposomes |
| Received:February 28, 2005 |
| DOI： |
| KeyWords:Boron neutron capture therapy Liposome Cellular targeting Cellular retention |
| FundProject:国家自然科学基金资助项目(30470501) |
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| Abstract:: |
| 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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