Reactive oxygen species generation via copper redox cycling in tumor microenvironment (CDT)

This target refers to the biochemical process of generating reactive oxygen species (ROS) through the redox cycling of copper ions within the tumor microenvironment (TME) (Tang et al., 2019, Angewandte Chemie). In this mechanism, copper ions transition between Cu(II) and Cu(I) states, a process often facilitated by high levels of intracellular reducing agents like glutathione (GSH) found in cancer cells (Wang et al., 2020, ACS Nano). The resulting Cu(I) reacts with endogenous hydrogen peroxide (H2O2) via Fenton-like reactions to produce highly toxic hydroxyl radicals (OH*) (Huo et al., 2017, Nature Communications). This localized ROS production causes extensive oxidative damage to cellular lipids, proteins, and DNA, ultimately triggering apoptosis or ferroptosis (Li et al., 2021, Coordination Chemistry Reviews). Drugs like disulfiram and elesclomol exploit this by forming copper complexes or shuttling copper into mitochondria to enhance oxidative stress (Kirshner et al., 2008, Molecular Cancer Therapeutics). Additionally, copper-based nanoparticles are being developed as chemodynamic therapy (CDT) agents to deliver copper specifically to the tumor site (Lin et al., 2018, Chemical Society Reviews). Despite its potential, the strategy faces challenges regarding the systemic toxicity of copper and the requirement for high H2O2 levels to ensure tumor selectivity (Ge et al., 2020, Advanced Materials).

Other names

Chemodynamic therapyCopper-mediated Fenton-like reactionCopper-induced oxidative stressCDTCopper redox cycling

Copper ions undergo redox cycling (Cu2+ to Cu+) facilitated by glutathione, followed by a Fenton-like reaction with hydrogen peroxide to generate hydroxyl radicals that induce oxidative cell death.