Ferrocene-Liposoime-PEG2000 Induces Ferroptosis In Cancer Cells

Ferroptosis is a new form of cell death presented by Dixon et al.at 2012,which is iron dependent and significantly different from the previously known cell death in terms of mechanism,cell morphology and biochemical indicators.Because of a unique physiological microenvironment of tumor tissue(over-expressed hydrogen peroxide,glutathione,and weak acidicity,etc.),an anti-cancer strategy based on the Fenton reaction to generate hydroxyl radicals to induce ferroptosis in cancer cells has been reported.However,there is a problem with this type of treatment strategy that the hydroxyl radical generated by the Fenton reaction is extremely annihilable,which has a short existence time of only 10-9 s.This problem causes that the hydroxyl radicals have insufficient time to destroy the physiological environment in the cancer cells and induce ferroptosis.And utilization efficiency of the hydroxyl radical is low and the anticancer effect is poor.It is worth noting that lipid peroxide plays an important role in the process of ferroptosis.There is a chain process of the oxidation reaction of lipid,induced by unsaturated double bonds of lipid attacked by radicals.And the chain progcess leads to continuous consumption of lipid and rupture of cell membrane.In addition,the LOOH formed during the reaction can also undergo Fenton-like reaction with ferrous.According to the above mechanisms,liposome is used herein to load ferrocene(Fc-Lp-PEG).Since tumor cells overexpress hydrogen peroxide,Fc-Lp-PEG can undergo Fenton reaction at such tumor cells to produce hydroxyl radical.The generated hydroxyl radical can directly react with the unsaturated lipd in situ to initiate the lipid oxidative chain reaction,resulting in improvement of utilization efficiency of the hydroxyl radical and enhancement of the reactive oxygen species level and the lipid peroxide level in the tumor cells.Finally,Fc-Lp-PEG can induce ferroptosis in the cancar cells and has the ability of anti-cancer.