Study of reactive oxygen species responsive unsaturated fatty acid liposomes promoting ferroptosis in tumor cells
Objective To prepare an arachidonic acid modified liposome(Lipo-DAPE)and to investigate the reactive oxygen species(ROS)responsiveness and cytotoxicity of Lipo-DAPE,as well as its ability to promote ferroptosis in tumor cells.Methods The formulation of Lipo-DAPE was optimized using hydrodynamic size and Zeta potential as evaluation indexes.The morphology,stability and other physicochemical properties along with the ROS responsiveness and drug release rate of liposomes were thoroughly characterized and investigated by transmission electron microscope and dynamic light scattering techniques.The cellular uptake of liposomes by 4T1 cells was observed with the aid of confocal laser scanning microscope.The cytotoxicity of Lipo-DAPE was evaluated by MTT assay.The variation of intracellular ROS,lipid peroxide and glutathione(GSH)level in tumor cells were detected to reflect the effect of Lipo-DAPE on promoting ferroptosis.Results The hydrodynamic diameter of Lipo-DAPE was(74.4±1.0)nm and the Zeta potential was(29.4±1.2)mV.This kind of liposome could maintain stability within 48 h and enable rapid cargo release upon ROS triggering in tumor microenvironment.Lipo-DAPE could be successfully internalized by 4T1 tumor cells and showed cytotoxicity due to lipid peroxidation.The increased amounts of ROS and lipid peroxides,and the decreased level of GSH after Lipo-DAPE treatment were significant.Conclusion This study provides a facile approach to enhance the efficacy of ferroptosis by using unsaturated fatty acid liposomes.It also provides a novel strategy and theoretical basis for the design of all-active drug delivery systems.
liposomesarachidonic acidreactive oxygen species responsivenessferroptosisdrug delivery
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