Ascorbate-Triggered Antitumor Activity of Nanoceria- and Ceria-Based Supramolecular Complexes in 2D and 3D Cell Cultures

Supramolecular complexes (SMCs) based on cholesterol, menadione, and redox-active ceria nanoparticles (NPs) with a pronounced antitumor effect triggered by the addition of ascorbic acid were obtained. Ascorbic acid plays the role of electron donor, increasing sufficiently the ability of ceria NPs in SMCs to oxidize thiol-containing biological molecules including glutathione and cysteine. The mechanism of the enhanced oxidizing ability of SMCs is based on the redox cycling of both ceria NPs and menadione with superoxide anions formed as an intermediate product. As a result of strong prooxidant activity, SMCs provide significant cytotoxicity toward mouse fibrosarcoma cells in 2D and 3D models accompanied by reduced cell viability, a decrease of the mitochondrial membrane potential, and cell shrinkage. The absence of such an effect on murine fibroblasts indicates that the cytotoxic action of an ascorbate-nanoceria pair is highly selective, targeting tumor cells but not nontumor ones.