Shedding light on brain tumours: testing the combination of photothermal therapy and 17-AAG in the treatment of glioblastoma multiforme

• Published in: Canadian journal of neurological sciences 2014-05, Vol.41 (3), p.S47-S47
• Main Authors: Ganesh, A, Nair, A K, Sheehan, K, Tekrony, A, Cramb, D T
• Format: Article
• Language: English
• ISSN: 0317-1671

Background: Glioblastoma Multiforme (GBM) treatment is limited by suboptimal surgical resection. Photothermal therapy (PTT) using light irradiation and gold nanoparticles (GNPs) may permit localized hyperthermic treatment. However, PTT is hindered by thermotolerance, facilitated by heat-shock proteins (HSPs). We hypothesized that the chemotherapeutic drug 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a HSP-90 inhibitor, would synergize with GNP-mediated PTT in GBM. Methods: 17-AAG and GNPs were delivered individually and in combination via dual-region loaded liposomes, to 90 wells of the WT U343 GBM cell line, with 12 control GBM wells. Treatment wells were irradiated using a 15W/cm2 500nm Light-Emitting Diode for 60 minutes. The viable cells were quantified using an Adenosine Tri-phosphate Bioluminescence Assay. Results: Direct light irradiation alone resulted in 6.6% cell lysis (95% confidence interval [CI] 5.4-8.2%). The addition of GNPs showed a limited improvement to 9.9% (95% CI 7.4-11.7%, P=0.007 versus light alone). 17-AAG by itself precipitated 68.8% lysis (95% CI 66.1-71.3%) and potentiated PTT even without GNPs, causing 75.9% lysis (95% CI 73.0-78.6%, P