A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells

Recent Advances in Hydrogen Peroxide Responsive Organoborons for Biological and Biomedical Applications

“…The reduction of 77 d by GSH forms glutathione disulfide and simultaneously release Cu(I) species, which significantly induces GSH depletion and ROS‐amplification, finally leading to redox imbalance of cancer cells. As a proof‐of‐concept, a combination of 77 a with Cu(II) demonstrated greater synergistic inhibition against HepG2 cervical carcinoma cells than normal L02 liver cells [81] …”

“…These boronate‐based prochelators can be selectively activated to release the active phenol counterpart preferentially to a local environment with elevated H 2 O 2 concentrations, therefore inducing site‐specific metal binding events. These ROS‐responsive prochelators have the potential to decrease oxidative injury only under the disease‐specific conditions associated with oxidative stress and minimize the undesirable off‐target metal‐chelate interactions leading to enhanced selectivity and improved therapeutic potential relative to the parent chelators [31,80,81] . There are two major categories of H 2 O 2 ‐responsive prochelators, i. e. Fe‐ or Cu‐based prochelators that are activated site‐specifically to form redox‐inactive Fe 3+ ‐ or Cu 2+ ‐complex, therefore blocking Fe‐ or Cu‐dependent and site‐specific production of HO .…”

“…As a proof-of-concept, a combination of 77 a with Cu(II) demonstrated greater synergistic inhibition against HepG2 cervical carcinoma cells than normal L02 liver cells. [81]…”

Selective Targeting of Cancer Cells by Copper Ionophores: An Overview

“…Some authors have invoked this aspect to explain the selectivity shown by some Cu ionophores, including DSF, CQ, and GTSM, towards cancer cells as discussed above (Safi et al, 2014;Denoyer et al, 2016;Dai et al, 2017;Ji et al, 2018). However, ROS susceptibility can be further exploited through systems activated by GSH or ROS with the concomitant depletion of antioxidants as suggested for CDT (Bao et al, 2018(Bao et al, , 2020.…”

A carrier free photodynamic oxidizer for enhanced tumor therapy by redox homeostasis disruption

“…24 Moreover, Nap as a neutral and lipophilic complex could coordinate with Cu 2+ to decrease the intracellular GSH levels and hinder the intracellular antioxidative system. 25,26 In light of the above considerations, a carrier-free photodynamic oxidizer was constructed for enhanced photodynamic tumor therapy by disrupting the redox homeostasis (Scheme 1). It was assumed that Nap could assemble with hydrophobic pyropheophorbide-a (Pyro) to prepare a nanosized photodynamic oxidizer (PyroNap) through intermolecular interactions with improved solubility and stability.…”