Anticancer Activity of Cell-Penetrating Redox Phospholipid Polymers

Redox-active molecules are promising anticancer compounds because cancer cells are vulnerable to oxidative stress. Anticancer drugs are often incorporated into synthetic polymers to improve water solubility, stability, and retention in the body. Most conventional redox-active polymers are regarded as stimuli-responsive polymers, which induce the release of anticancer drugs in response to the surrounding redox environment. Here, we prepared redox phospholipid polymers composed of 2-methacryloyloxyethyl phosphorylcholine units and ferrocene or quinone units as anticancer redox polymers. Redox phospholipid polymers can disturb the intracellular redox state owing to their redox activity and cell membrane permeability. We observed that the redox potential of the polymers affected the reactivity with intracellular redox species and O₂, resulting in a different impact on the viability of human cancer and normal cells. Notably, the polymer with moderate reactivity with the intracellular redox species and O₂ was shown to suppress the viability of the cancer cells selectively.