Program Information
In Vitro Demonstration of Endothelial Dose Enhancement Due to Gold Nanoparticles During Low-Voltage Radiotherapy
S Yasmin-Karim1*, M Moreau1,2 , R Kumar1,3 , GM Makrigiorgos1 , J Hanlon4 , M Arnoldussen4 , J Hempstead5 , J Celli5 , W Ngwa1,2 , (1) Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, (2) University of Massachusetts Lowell, Lowell, MA, (3) Northeastern University, Boston, MA, (4) Oraya Therapeutics inc., Newark, CA, (5) University of Massachusetts Boston, Boston, MA
Presentations
SU-G-TeP3-5 (Sunday, July 31, 2016) 5:00 PM - 5:30 PM Room: ePoster Theater
Purpose: Oraya Therapy uses low-voltage, stereotactic, highly targeted X-rays for the treatment of wet age-related macular degeneration (AMD) — offering a new option for patients worldwide. Neovascular endothelial cells play a crucial role in the pathogenesis of this disease. This in-vitro study investigates the potential of gold nanoparticles (GNP) to enhance endothelial cell damage during low-voltage radiotherapy towards potential applications in the treatment of wet-AMD.
Methods: Primary human umbilical cord vein endothelium cells (HUVEC) were treated with 1.4 nm sized GNPs for 24 hrs and then irradiated with variable X-ray doses using an Oraya therapy system (100 kVp) or a Small Animal Radiation and Research platform (SARRP) at other beam qualities (up to 220 kVp). Radio-sensitization was assessed by clonogenic assays. Variable concentrations of GNPs (0.05 mg/ml, 0.1 mg/ml, 0.25 mg/ml, 0.5 mg/ml, and 1 mg/ml) where employed. The dose enhancement factor (DEF) was calculated as the ratio of radiation doses required to give the same biological effect (survival factor, SF) with and without GNPs.
Results: Preliminary results show DEFs of up to 2.62 for the different combinations of x-ray doses and GNP concentrations and beam qualities. In general the DEF increased with increase in GNP concentration. However, for high doses the effect of GNP becomes less apparent likely due to already high cell kill by the radiation alone.
Conclusion: The findings suggest that targeted GNPs can play a significant synergistic role in enhancing stereotactic radiosurgery for wet AMD. The results also provide impetus for ongoing studies to find the optimal synergy between the doses or beam energies and GNPs concentration. This will benefit in-vivo studies towards development of nanoparticle-aided radiotherapy for treatment of wet-AMD and potentially ocular cancers.
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