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

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.