Abstract
Stable Au (III) and Au (I) complexes, including cyclometallated gold complex, are promising candidates for anticancer drugs that exhibit potent in vitro and in vivo antitumor activities against human carcinoma xenografts tumors. Herein, a supramolecular synthesis route was presented for hierarchical self-assembly of coordinated adenine-Au (III) complexes into colloidal nanoparticles. During the polymerization process, the addition of adenosine triphosphate (ATP) and thiolated poly(ethylene glycol) was found to greatly improve the particle size control as well as the colloidal stability to against demetallation in physiological conditions. ATP taken up about 8% of coordinated Au-nanoparticles and mostly on the surface . However, the as-prepared colloidal Au-nanoparticles could be easily decomposed in high glutathione (GSH) levels, leading to a fast release inside living tumor cells. When incubated with cancer cells, the coordinated Au-nanoparticles displayed a significant in vitro antitumor effect with low IC50 value (~48 uM). Apoptosis analysis also confirmed that the nanoparticulate formulation promoted a higher cell dead rate of cancer cells than Au ions with the same dose. The relation of intracellular GSH concentration to Au-nanoparticles was found by pretreatment of GSH inhibitor. Photosensitizer were furthermore incorporated into the supramolecular assemblies and an increased Au-based therapeutic efficacy for prostate cancers treatment was successfully achieved . Overall, these nanoparticulate Au-bearing complexes represent an attractive alternative to overcome the failure of cisplatin resistance in traditional chemotherapy.