Positively charged, phenolic hydroxyl and anthraquinone structured polystyrene microspheres targeting dual elimination of bacterial pathogens and pathogen-associated molecular patterns for sepsis therapy.

During bacterial infection in sepsis, both the bacteria and pathogen-associated molecular patterns (PAMPs, including endotoxins and exotoxins) contribute to the progression of sepsis. Traditional single-target bactericidal therapies commonly prove ineffective against sepsis, particularly during the hyperinflammatory phase. This work develops a hemoperfusion adsorbent microsphere for the treatment of sepsis via simultaneously clearing bacterial pathogens and their subsequently released PAMPs. Styrene, 2-(dimethylamino)ethyl methacrylate (DMAEMA) and precisely modified aloe emodin (AED) are polymerized, and the PS-DMAEMA-AED (PSQAE) microspheres are then prepared via a liquid-liquid phase inversion method. The PSQAE microspheres eliminate 98.4% of Staphylococcus aureus (S. aureus) and 95.7% of Escherichia coli (E. coli) within 3 h. Furthermore, the PSQAE microspheres significantly reduce exotoxin-induced hemolysis (from 93% to 5.1%) by neutralizing bacterial toxins and lower endotoxin levels (from 72.7 EU per mL to 13.9 EU per mL). Besides, the PSQAE microspheres protect A549 cells from exotoxin damage, reducing mortality from 92.1% to 9%, and restore pro-inflammatory cytokine concentrations to levels comparable to those of healthy cells. In a septic blood model, the PSQAE microspheres also significantly attenuate red blood cell hemolysis ratio and pro-inflammatory cytokine concentrations. Notably, we further investigate the strong interaction between PSQAE and α-toxin via molecular simulation techniques, revealing a binding energy of -5.138 kcal mol-1. In summary, this work establishes a comprehensive blood purification strategy for sepsis that combines bacterial clearance, neutralization of bacterial virulence factors, and inflammatory modulation.