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EGF-receptor targeted liposomes with boronated acridine: growth inhibition of cultured glioma cells after neutron irradiation
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
NCI / NIH USA.
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2005 (Engelska)Ingår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 81, nr 8, s. 621-629Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
2005. Vol. 81, nr 8, s. 621-629
Nyckelord [en]
Boron neutron capture therapy (BNCT), Epidermal growth factor (EGF), liposome, acridine, clonogenic cell survival
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-104628DOI: 10.1080/09553000500332137PubMedID: 16298943OAI: oai:DiVA.org:uu-104628DiVA, id: diva2:220027
Tillgänglig från: 2009-05-29 Skapad: 2009-05-29 Senast uppdaterad: 2018-12-04

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Malmström, Per-UnoGedda, Lars

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