Erika Bohl Kullberg1, Marika Nestor, Lars Gedda. 1. Division of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala, Sweden. Erika.Bohl@bms.uu.se
Abstract
PURPOSE: The aim of this work was to investigate the cellular binding and processing of polyethylene glycol-stabilized epidermal growth factor (EGF) liposomes. The liposomes were actively loaded with water-soluble boronated acridine (WSA), primarily developed for boron neutron capture therapy. METHODS: The uptake, internalization, and retention of EGF-liposome conjugates were studied in two cultured monolayer cell-lines, A-431 and U-343, with regard to the nuclide-label on the targeting agent, the carrier, and the load. The subcellular localization of WSA was studied using confocal microscopy. RESULTS: We found that the liposome complex was internalized after specific binding to the EGF receptor. After internalization in the tumor cells, WSA was distributed mainly in the cytoplasm and was shown to have long cellular retention, with 80% of the boron remaining after 48 h. CONCLUSIONS: The long retention of the compound and the cellular boron concentration reached makes these targeted liposomes interesting for further development toward boron neutron capture therapy.
PURPOSE: The aim of this work was to investigate the cellular binding and processing of polyethylene glycol-stabilized epidermal growth factor (EGF) liposomes. The liposomes were actively loaded with water-soluble boronated acridine (WSA), primarily developed for boron neutron capture therapy. METHODS: The uptake, internalization, and retention of EGF-liposome conjugates were studied in two cultured monolayer cell-lines, A-431 and U-343, with regard to the nuclide-label on the targeting agent, the carrier, and the load. The subcellular localization of WSA was studied using confocal microscopy. RESULTS: We found that the liposome complex was internalized after specific binding to the EGF receptor. After internalization in the tumor cells, WSA was distributed mainly in the cytoplasm and was shown to have long cellular retention, with 80% of the boron remaining after 48 h. CONCLUSIONS: The long retention of the compound and the cellular boron concentration reached makes these targeted liposomes interesting for further development toward boron neutron capture therapy.
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