EGF-receptor targeted liposomes with boronated acridine: growth inhibition of cultured glioma cells after neutron irradiation.

Abstract

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.

• Authors: Erika Bohl Kullberg, Qichun Wei, Jacek Capala, Valerio Giusti, Per-Uno Malmström, Lars Gedda
• Journal: International journal of radiation biology (Int J Radiat Biol) Vol. 81 Issue 8 Pg. 621-9 (Aug 2005) ISSN: 0955-3002 [Print] England
• PMID: 16298943 (Publication Type: Journal Article)

Chemical References

• Liposomes
• ErbB Receptors

Topics

• Boron Neutron Capture Therapy
• Brain Neoplasms (pathology)
• Cell Proliferation
• Cell Survival
• ErbB Receptors (physiology, radiation effects)
• Glioma (pathology)
• Humans
• Liposomes
• Neutrons
• Tumor Cells, Cultured