Amplification of Lipid Peroxidation by Regulating Cell Membrane Unsaturation To Enhance Chemodynamic Therapy

Abstract Lipid peroxidation (LPO) is one of the most damaging processes in chemodynamic therapy (CDT). Although it is well known that polyunsaturated fatty acids (PUFAs) are much more susceptible than saturated or monounsaturated ones to LPO, there is no study exploring the effect of cell membrane unsaturation degree on CDT. Here, we report a self‐reinforcing CDT agent (denoted as OA@Fe‐SAC@EM NPs), consisting of oleanolic acid (OA)‐loaded iron single‐atom catalyst (Fe‐SAC)‐embedded hollow carbon nanospheres encapsulated by an erythrocyte membrane (EM), which promotes LPO to improve chemodynamic efficacy via modulating the degree of membrane unsaturation. Upon uptake of OA@Fe‐SAC@EM NPs by cancer cells, Fe‐SAC‐catalyzed conversion of endogenous hydrogen peroxide into hydroxyl radicals, in addition to initiating the chemodynamic therapeutic process, causes the dissociation of the EM shell and the ensuing release of OA that can enrich cellular membranes with PUFAs, enabling LPO amplification‐enhanced CDT.