EGF-receptor targeted liposomes with boronated acridine: growth inhibition of cultured glioma cells after neutron irradiation
2005 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 81, no 8, 621-629 p.Article in journal (Refereed) Published
PURPOSE: To study survival of cultured U-343MGaCl 2:6 glioma cells after incubation with boron-containing liposomes targeting the epidermal growth factor receptor following neutron irradiation. MATERIALS AND METHODS: Epidermal growth factor-tagged liposomes were loaded with water-soluble boronated acridine developed for boron neutron capture therapy, (BNCT). Cellular uptake and distribution were studied. Further, cells were placed at 3 cm depth in a phantom and exposed to an epithermal neutron beam to study clonogenic cell survival. RESULTS: The cellular uptake of boron reached 90 ppm and it was determined by subcellular fractionation that most of the cell-associated boron was located outside of the nucleus. For clonogenic survival, the cells were incubated with epidermal growth factor receptor-targeted liposomes for 4 hours resulting in a cellular concentration of 55 ppm boron (11 ppm 10B). At a fluence of 3 x 10(12) neutrons/cm2 the cell killing effect of the boron-containing epidermal growth factor-liposomes was about ten times higher than for neutrons only. Furthermore, theoretical calculation of the survival by enriched compound (55 ppm 10B), using the parameters from non-enriched compound (11 ppm 10B), shows that the killing effect in this case would be approximately five orders of magnitude higher than for neutrons only. CONCLUSION: The results in this study show that epidermal growth factor-receptor targeted liposomes are suitable as tumor-cell delivery agents of boron for BNCT and support further studies to demonstrate their effectiveness in vivo.
Place, publisher, year, edition, pages
2005. Vol. 81, no 8, 621-629 p.
Boron neutron capture therapy (BNCT), Epidermal growth factor (EGF), liposome, acridine, clonogenic cell survival
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-104628DOI: 10.1080/09553000500332137PubMedID: 16298943OAI: oai:DiVA.org:uu-104628DiVA: diva2:220027