Erythroliposomes: Integrated Hybrid Nanovesicles Composed of Erythrocyte Membranes and Artificial Lipid Membranes for Pore-Forming Toxin Clearance

Abstract

Pore-forming toxins (PFTs) are the most common bacterial virulence proteins and play a significant role in the pathogenesis of bacterial infections; thus, PFTs are an attractive therapeutic target in bacterial infections. Inspired by the pore-forming process and mechanism of PFTs, we designed an integrated hybrid nanovesiclethe erythroliposome (called the RM-PL)for PFT detoxification by fusing natural red blood cell (RBC) membranes with artificial lipid membranes. The lipid and RBC membranes were mutually beneficial when integrated into a hybrid nanovesicle structure. The RBC membrane endowed RM-PLs with the capacity for detoxification, while the PEGylated lipid membrane stabilized the RM-PLs and greatly improved the detoxification capacity of the RBC membrane. With α-hemolysin (Hlα) as a model PFT, we demonstrated that RM-PLs could not only significantly reduce the toxicity of Hlα to erythrocytes in vitro but also effectively sponge Hlα in vivo and rescue mice from Hlα-induced damage. Moreover, the high detoxification capacity of RM-PLs was shown to be partly related to the expression of the Hlα receptor protein, a disintegrin and metalloproteinase domain-containing protein 10 on the RBC membrane. Consequently, as a component integrating natural and artificial materials, the erythroliposome nanoplatform inspires potential strategies for antivirulence therapy.

Hybrid Erythrocyte Liposomes: Functionalized Red Blood Cell Membranes for Molecule Encapsulation

“…The protocol presented in this work allows the efficient preparation of hybrid erythrocyte membranes. Our data indicate that synthetic lipid molecules can be incorporated into RBC membranes and show no indication of phase separation, in contrast to previously published protocols 18. The crucial intermediate step in the protocol is the preparation of solid supported hybrid membranes.…”

“…However, controlling membrane morphology and structure is essential in generating applicable carrier systems. Recent papers18–20 used a combination of biological and synthetic membranes. Human erythrocytes are well suited as a base for such hybrid liposomes as their membrane can be easily isolated from other cellular components.…”

“…The biocompatibility of RBC based drug delivery systems is a long standing concern. While the hybrid membranes are entirely composed of biocompatible materials,18 previous studies have shown that loading of RBCs can have a significant impact on their biocompatibiliy 16,17. This is, however, often a result of heavy modifications to the RBC surface.…”

“…Although RBCs have numerous advantages over the aforementioned synthetic drug carriers, loaded RBCs or RBC ghosts typically lack specificity with respect to target sites or show a reduced biocompatibility 16,17. To address these difficulties, recent approaches include hybrid RBC liposomes as drug carriers,18 or combined membranes from multiple endogenous cells 19,20…”

Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy

“…Specialized NP platforms have been developed with tailored functionalities by coating the NP core with hybrid membranes, formed by fusing natural membranes from different types of cells. For instance, NPs have been functionalized with hybrid membranes obtained by fusing membrane materials obtained from different cell types such as cancer cells and RBCs [49], RBCs, and platelets [50], and RBCs and artificial membranes [51]. However, NPs functionalized with a hybrid membrane combining the membrane materials of macrophages and cancer cells have not been fabricated.…”