April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Evaluation of the Efficacy of Topotecan Loaded Au-Tethered Liposomes and AU-011 for the Treatment of Retinoblastoma in vitro
Author Affiliations & Notes
  • Kristen Jijelava
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Shin Kang
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Uday Kompella
    Pharmaceutical Sciences, University of Colorado, Denver, CO
  • Shelley Ann Durazo
    Pharmaceutical Sciences, University of Colorado, Denver, CO
  • Elisabet de los Pinos
    Aura Biosciences, Cambridge, MA
  • John MacDougall
    Aura Biosciences, Cambridge, MA
  • Hans E Grossniklaus
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Footnotes
    Commercial Relationships Kristen Jijelava, None; Shin Kang, None; Uday Kompella, None; Shelley Durazo, None; Elisabet de los Pinos, Aura Biosciences (E); John MacDougall, Aura Biosciences (E); Hans Grossniklaus, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3072. doi:
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      Kristen Jijelava, Shin Kang, Uday Kompella, Shelley Ann Durazo, Elisabet de los Pinos, John MacDougall, Hans E Grossniklaus; Evaluation of the Efficacy of Topotecan Loaded Au-Tethered Liposomes and AU-011 for the Treatment of Retinoblastoma in vitro. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3072.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

The purpose of the study is to test our hypothesis that if WERI-Rb-1 cells are exposed to topotecan, topotecan loaded Au-tethered DPPC/DPGPTE liposomes treated with near-infrared (NIR) pulsed laser, or AU-011 treated with a light-emitting diode (LED) laser, that the result will be cell death.

 
Methods
 

WERI-Rb-1 cells were grown to 3-4x10^5 cells/mL and exposed to different concentrations of topotecan (5-20 µg/50 µL) and topotecan loaded Au-tethered DPPC/DPGPTE liposomes (10-50 µg/50 µL). After treatment with topotecan loaded Au-tethered DPPC/DPGPTE liposomes, the cells were exposed to an 810 nm diode laser (1500 mW, 1000 msec at 50 msec repeat intervals) for 2 minutes. Similarly, WERI-Rb-1 cells were treated with multiple concentrations of AU-011 (Human papillomavirus virus-like particles conjugated with IR700 dye) (0.1-3 nM) and exposed to 16J of light using a LED lamp. Cell viability was determined at multiple time points using a trypan blue viability stain and a hemocytometer.

 
Results
 

Topotecan at a concentration of 20 µg/50 µL causes 99.7% cell death (p<0.001) by 4 hours. There was no statistically significant difference in cell viability rates at any time point between the 20 µg/50 µL of topotecan loaded Au-tethered DPPC/DPGPTE liposome groups that received NIR pulsed laser therapy as compared to the same group that did not receive laser therapy. The AU-011 at 0.1 nM, 1 nM, and 3 nM concentrations following exposure to 16J with an LED lamp all resulted in a statistically significant (p < 0.05) increases in cell death (83.3-91.7%, 87.5-100%, and 95.0-100% respectively) compared to the control (1.56-8.75% dead cells) at 1, 4, and 24 hours.

 
Conclusions
 

Topotecan at a concentration of 20 µg/50 µL effectively and rapidly kills WERI-Rb-1 cells in vitro. NIR pulsed laser therapy applied for a clinically relevant duration does not cause the necessary rise in temperature of the gold nanoshells to induce the release of a significant amount of topotecan from the liposomes. However, AU-011 in combination with LED therapy presents a promising novel method to effectively induce cell death of retinoblastoma cells locally without being cytotoxic to cells that do not receive LED exposure.

     
Keywords: 703 retinoblastoma • 607 nanotechnology • 624 oncology  
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