Ultrasound responsive erythrocyte membrane-derived hybrid nanovesicles with controlled drug release for tumor therapy

Abstract

An ultrasound responsive erythrocyte membrane-derived hybrid nanovesicle drug delivery system (DOX/HMME@FA-NL) is constructed by the membrane fusion functionalization strategy for controlled drug release and enhanced tumor therapy. The reliability and effectiveness of the membrane fusion strategy are confirmed through characterization of the particle size and zeta potential, Förster energy resonance transfer and fluorescence co-localization analyses. The DOX/HMME@FA-NL could be triggered for reactive oxygen species (ROS) generation under ultrasound stimulation. And the unsaturated phospholipids in DOX/HMME@FA-NL can be oxidized by ROS, leading to the destruction of the structure of the hybrid membrane to achieve the controlled release of drugs, thereby enhancing their tumor cell killing effect. Besides, the linkage of the folate targeting group also enhances the tumor targeting ability of DOX/HMME@FA-NL. H22 tumor-bearing mice were intravenously injected with DOX/HMME@FA-NL and treated with ultrasound, they achieved better than expected tumor sonodynamic response treatment effects.