title: Introductory experiments on ligand liposomes as delivery agents for boron neutron capture therapy.
abstract: Liposomes are, when coupled to receptor ligands, candidates for receptor mediated delivery of boron for tumour therapy since they have capacity to deliver large amounts of boron per receptor interaction. With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting. In the case of WSA1 a ligand dependent uptake was obtained and the boron uptake was as good as if free WSA1 was given. No ligand dependent boron uptake was seen for WSP1 containing liposomes. Thus, WSA1 is a candidate for further studies. Approximately 10(5) boron atoms were in each liposome. A critical assessment indicates that after optimization up to 10(6) boron atoms can be loaded. Since it is known that, for therapeutic effect, approximately 10(8)-10(9) boron atoms are needed in a single tumour cell it is realized that 10(2)-10(3) receptor interactions are needed to meet the demand. Tests applying cultured glioma cells indicate, without optimization of the delivery conditions, a boron uptake in the ppm range, which is necessary for successful BNCT. Thus, it seems possible to kill micro-invasive tumour cells with targeted liposomes if the delivery conditions are optimal.
authors.affiliation: Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden. ErikaBohl@bms.uu.se
authors.forename: Erika
authors.initials: E
authors.lastname: Bohl Kullberg
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Edwards
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.forename: Stefan
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
mesh_terms: D000166:Acridines / Q000008:administration & dosage; D001896:Boron Compounds / Q000008:administration & dosage*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008024:Ligands; D008081:Liposomes; D011092:Polyethylene Glycols / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000166:Acridines; D001896:Boron Compounds; D008024:Ligands; D008081:Liposomes; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D066246:ErbB Receptors