Scientists report on the development of a radioactive gold nanoparticle for prostate cancer therapy that they claim is far less toxic to normal tissues than traditional radiation therapy and results in massive reduction in tumor volume and increased survival in experimental mice after just one dose. The nanoparticles, derived from the Au-198 isotope, incorporate an extract from green tea known as epigallocatechin-gallate (EGCg), which effectively latches the nanoparticles onto the prostate tumor cells and facilitates their internalization.
The tumor-targeting EGCg actually has a dual function, the University of Missouri, Columbia-led team reports. Firstly, the redox chemistry of the phytochemical plays a key role in formulation of the biocompatible 198AuNPs, as it converts gold salt into stable gold nanoparticles. Secondly, the green tea extract directly and selectively binds with laminin67R receptors that are overexpressed in prostate tumor cells.
Reported in PNAS, the team’s work with the β-emitting gold nanoparticles (198AuNPs-EGCg) demonstrated that following injection into a prostate tumor the vast majority of the particles were retained within the tumor itself, and rapidly internalized by the tumor cells. This retention was facilitated by the high affinity of the EGCg for laminin67R, and also by the size of the nanoparticles, which prevented them from escaping the tumor and entering surrounding tissues.
Notably, the β radiation emitted by the 198AuNPs-EGCg particles has a range of about 11 mm, which is far reaching enough to zap prostate tumor cells directly surrounding the administration site, but not far reaching enough to subject more distant healthy tissue to radiation, they state. And with a half life of 2.7 days, radioactivity from the gold nanoparticles lasts for less than three weeks.
To test therapeutic efficacy of the 198AuNPs-EGCg in vivo the researchers established a unilateral flank model of prostate cancer derived from human PC-3 cells in SCID mice. The animals were then given just one intratumoral dose of the nanoparticles. The results showed that treatment resulted in tumor shrinkage within just one week, and by three weeks the average tumor volume in the treated animals was 80% less than the tumor volume in control animals. Analysis of the treated tumors showed that over 70% of the injected dose of 198AuNP-EGCg was retained at the tumor site, and the nanoparticles were taken up in high concentrations by the tumor cells. Importantly, there was no evidence of toxicity to other tissues, and the treatment appeared to be well tolerated.
Kattesh V. Katti, M.D., Ravi Shukla, M.D., and colleagues detail their studies in a paper titled “Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer.”
“Interaction of biocompatible EGCg with 198Au precursor affords the production of inherently therapeutic gold nanoparticles through a novel synthetic route, effectively eliminating toxic chemicals that are routinely utilized in pharmaceutical formulations,” the authors conclude. “This novel intratumorally injectable 198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.”