The Atomically Precise Gold/Captopril Nanocluster Au<sub>25</sub>(Capt)<sub>18</sub> Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation
Kaushik Bhattacharya, Kaushik Bhattacharya, Vanessa Joanne Xavier, Abolfazl Ziarati, Didier Picard, Thomas Bürgi
Abstract
(GNC), respectively. We demonstrated that a change of the ligand of the cluster completely changes its biological functions. Whereas both nanoclusters are capable of internalization, only CNC exhibits remarkable cytotoxicity, more specifically on cancer cells. CNC shows enhanced cytotoxicity by inhibiting the OXPHOS of mitochondria, possibly by inhibiting the ATP synthase complex of the electron transport chain (ETC), and by initiating the leakage of electrons into the mitochondrial lumen. The resulting increase in both mitochondrial and total cellular ROS triggers cell death indicated by the appearance of cellular markers of apoptosis. Remarkably, this effect of nanoclusters is independent of any external light source excitation. Our findings point to the prevailing importance of the ligand shell for applications of atomically precise nanoclusters in biology and medicine.