Poster Presentation 28th Lorne Cancer Conference 2016

Stability After Storage of a Gold Nanoparticle-Docetaxel Conjugate Assessed by Breast Cancer Cell Killing (#296)

Nada Ahmed Alzahrani 1 , Norah Algamdi 2 , Joe Shapter 2 , Barbara Joanne Sara Sanderson 1
  1. Medical Biotechnology, School of Medicine, Flinders University, Adelaide, SA, Australia
  2. Flinders Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Adelaide, SA, Australia

Chemotherapy is often used for breast cancer, however a problem is delivering sufficient drug dose to the cancer cells without adverse effects on normal cells. A potential solution is targeted gold nanoparticles (AuNPs) conjugated to cancer drugs for delivery. We studied the stability of AuNPs conjugated to Docetaxel (AuNP-DTX), sampled during storage over 19 weeks. The AuNPs-DTX were stored in three solvents (Dimethylsulfoxide, DMSO, Ethanol, EtOH, Phophate buffered Saline, PBS), at three different temperatures (4°C, 25°C, and 20°C). Stability was monitored using the MTT colorimetric cytotoxicity assay to detect changes over time in effectiveness of stored AuNP-DTX at killing the human breast cancer cell line T47D. The hypothesis was that a particular solvent at a given temperature, would provide a stable storage condition for the AuNP-DTX and would therefore result in minimal loss of stability and activity of the AuNP-DTX despite increasing storage time. DMSO was the best solvent for maintaining a stable drug conjugate at all three temperatures 4°C, 25°C, and-20°C. Prior to storage (week 0) the AuNP-DTX had high activity and there was a decrease in relative survival to 50% for treatment with 10 and 0.01 ρM AuNP-DTX. After storage at 4°C, 25°C or -20°C for one week in DMSO, there was less cell killing, and relative survival decreased to 70-80% for 10 and 0.01 ρM of AuNP-DTX. After 19 weeks in DMSO, following storage at 4°C, 25°C or -20°C, relative survival was 90% -102% at 0.01 ρM. AuNP-DTX were next most stable when stored in EtOH compared to DMSO. However, AuNP-DTX stored in PBS at any of the three temperatures were not stable, and lost cell killing capacity at the range of doses tested, resulting in relative survival of ~100% or greater by week 1. Additional data from treatment with 5 doses from samples taken over 19 weeks for all storage will be presented. In conclusion, this study indicates that gold nanoparticles conjugated to Docetaxel are more stable when stored in DMSO or EtOH as solvents. Such storage conditions assist the preservation of the capacity of the conjugate to kill breast cancer cells. This work provides useful information for making decisions related to the choice of solvents compatible with Docetaxel powder for storage and subsequent use as a drug.