Erythrocyte membrane‐coated nanoparticles with toxin neutralization and antimicrobial activity

Abstract Bacterial infections pose a persistent threat to human health. Pore‐forming toxins (PFTs) secreted by pathogens lead to cell lysis, tissue damage, and systemic inflammation during infection. To address this challenge, we engineered a dual‐functional, PFT‐responsive nanoparticle platform (Q@RBC‐NP) consisting of α‐GPC‐PLA polymer core loaded with quercetin (a natural flavonoid with antimicrobial activity) and an erythrocyte (RBC) membrane shell. Physicochemical characterizations (dynamic light scattering, scanning electron microscopy, transmission electron microscopy) confirmed Q@RBC‐NP's core‐shell structure (162 nm), stable colloidal property (no significant size change over 10 days), and successful RBC membrane coating (zeta potential shifted to −19 mV). Hemolysis assays demonstrated Q@RBC‐NP broadly neutralized S. aureus α‐toxin and E. coli α‐hemolysin, reducing hemolysis from ~98% to 1%–2%. Dialysis studies revealed PFT‐triggered quercetin release: ~70%–75% of quercetin was released within 40 h in the presence of PFTs, compared to only 24% without PFTs. Antibacterial tests (colony‐forming unit counting, live/dead staining) demonstrated Q@RBC‐NP inhibited E. coli and S. aureus (6.4 mg/mL: 4.0%–5.8% bacterial survival). MTT assays confirmed good biocompatibility (HeLa/HEK293 cell viability >90%), and Q@RBC‐NP protected HEK293 cells from bacterial toxin damage. This platform integrates PFT neutralization and site‐specific antimicrobial delivery, offering a promising strategy against drug‐resistant bacterial infections.