Phospholipid-modified FeOCl Nanosheets For Tumor Therapy Based Upon Reactive Oxygen Species

As a newly discovered mechanism of cell death,ferroptosis is gradually showing its excellent application potential in tumor therapy.Elevated intracellular ROS is one of the distinguishing characteristics of ferroptosis.Due to the acidity and the overexpression of H2O2 in the microenvironment of tumor area,Fenton reaction is applied to generate ·OH for increasing the level of intracellular ROS and induce ferroptosis.This has become an effective antineoplastic protocol.As an important part of biofilm,phospholipids are also widely used in tumor therapy due to their excellent biocompatibility.In addition,unsaturated phospholipids are prone to generate a large amount of lipid peroxides by lipid peroxidation.Inspired by ferroptosis and lipid peroxidation chain reaction,FeOCl nanosheets was used as an iron source for Fenton reaction.Phospholipid was modified on surface of FeOCl to improve its stability and enhance its ability to generate ROS in tumor cells.The main research contents are as follows:FeOCl nanosheets were prepared by solid-phase method,and modified with polyacrylic acid and phospholipid to obtain FeOCl@PAA-Lip nanosheets.Based on the characteristics of the tumor microenvironment,the nanosheets can generatr ·OH through homogeneous and heterogeneous Fenton reactions due to the presence of FeOCl.Because of the modification of unsaturated phospholipids on the surface of FeOCl@PAA-Lip nanosheets,the generated·OH can oxidize them "in situ" to generate lipid peroxides,and initiate lipid peroxidation chain reaction,generating more ROS.On the one hand,based on the annihilation characteristics of ·OH,converting it to lipid peroxide can effectively reduce its annihilation and improving the utilization rate of·OH.On the other hand,the lipid peroxidation chain reaction which was induced by·OH produces a large amount of lipid peroxides,which raise the level of intracellular ROS and enhance the ferroptosis.The FeOCl@PAA-Lip nanosheets prepared in this paper own good stability,significant Fenton reaction effect,and excellent lipid peroxidation performance.It has no obvious toxicity to normal cells,but can kill most tumor cells under certain conditions.Animal experiment data shows that the FeOCl@PAA-Lip nanosheets prepared in this paper can effectively inhibit the growth of tumors.