In vivo evaluation of EGCG stabilized gold-198 nanoparticles in prostate cancer bearing mice

Objectives In this study we investigated Au-198 nanoparticles (198AuNP) that were rapidly produced using (-)-Epigallocatechin gallate (EGCG) an antioxidant reducing agent derived from green tea.

Methods The 198Au was produced at MURR and provided as H198AuCl4 in a final concentration of 0.05 M HCl. EGCG was dissolved in Milli-Q water, and the H198AuCl4 and carrier HAuCl4 (0.1 M Au) were added and stirred at room temperature for 5 min to generate the nanoparticles. The UV/Vis spectrum showed the expected Plasmon peak at 529-535 nm. TLC confirmed that over 99% of the gold was present in the nanoparticle form. SCID mice bearing human prostate cancer derived from PC-3 cells were used for pharmacokinetic and therapy studies. On day 6, 30 µL of EGCG 198AuNP (136 µCi) was injected into the tumor (IT) to deliver an estimated 70 Gy. Control animals received 30 µL of Dulbecco’s PBS. A further set of animals were injected IT with 30 µL of solution containing only EGCG. Tumors were measured twice weekly.

Results Previous results indicated IT injections result in the highest retention of activity in the tumor and lowest dose to normal tissues. In the pharmacokinetic studies animals injected with EGCG 198AuNP showed 77.8 ± 12.3 % ID was retained in the tumor at 30 min and 72.4 ± 13.0 % ID after 24 hr. Based on these results radiotherapy evaluations were conducted. No differences were noted between the controls and animals injected IT with EGCG. By day 18, tumors in the control group were 4-fold larger than those of the treatment group (p=0.04). By day 28, tumors in the control group were over 5-fold larger than those of the treatment group (p=0.01). An end of study biodistribution on day 42 showed 34.1 ± 19.8 %ID remained in the residual tumor.

Conclusions Using EGCG, 198AuNP can be formulated at room temperature to treat prostate cancer. The formed 198AuNP showed very good tumor retention and significantly inhibited tumor growth compared to saline controls and EGCG alone.

Research Support R01CA119412-0