Tumor-cell targeted epiderimal growth factor liposomes loaded with boronated acridine: uptake and processing.
OBJECTIVE
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.
Kullberg
Erika Bohl
EB
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
Nestor
Marika
M
Gedda
Lars
L
D000166:Acridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D000166:Acridines; D001896:Boron Compounds; D008081:Liposomes; D004815:Epidermal Growth Factor