Positively charged, phenolic hydroxyl and anthraquinone structured polystyrene microspheres targeting dual...

Area of Science:

• Biomaterials Science
• Infectious Disease Treatment
• Sepsis Pathophysiology

Background:

• Sepsis progression involves bacteria and pathogen-associated molecular patterns (PAMPs), including endotoxins and exotoxins.
• Conventional single-target therapies are often insufficient, especially during the hyperinflammatory phase of sepsis.
• A comprehensive approach is needed to address both bacterial load and toxic mediators in sepsis.

Purpose of the Study:

• To develop and evaluate a novel hemoperfusion adsorbent microsphere for simultaneous clearance of bacterial pathogens and PAMPs in sepsis.
• To investigate the efficacy of these microspheres in neutralizing bacterial toxins and reducing endotoxin levels.
• To assess the protective effects of the microspheres on cells and in septic blood models, and to elucidate the binding mechanism with bacterial toxins.

Main Methods:

• Polymerization of styrene, DMAEMA, and modified aloe emodin to create PS-DMAEMA-AED (PSQAE) microspheres via liquid-liquid phase inversion.
• In vitro assessment of bacterial clearance (Staphylococcus aureus, Escherichia coli), exotoxin neutralization, and endotoxin reduction.
• Evaluation of cell protection (A549 cells) against exotoxin damage, modulation of cytokine levels, and testing in a septic blood model.
• Molecular simulation to investigate the interaction between PSQAE microspheres and alpha-toxin.

Main Results:

• PSQAE microspheres achieved high clearance rates for S. aureus (98.4%) and E. coli (95.7%) within 3 hours.
• Significant reduction in exotoxin-induced hemolysis (93% to 5.1%) and endotoxin levels (72.7 EU/mL to 13.9 EU/mL).
• Demonstrated protection of A549 cells from exotoxin damage (mortality reduced from 92.1% to 9%), restoration of cytokine levels, and attenuation of hemolysis in a septic blood model.
• Molecular simulations revealed a strong binding interaction between PSQAE and alpha-toxin with a binding energy of -5.138 kcal mol⁻¹.

Conclusions:

• The developed PSQAE microspheres offer a dual-action strategy for sepsis treatment by removing bacteria and neutralizing virulence factors.
• This hemoperfusion approach effectively modulates the inflammatory response and protects against sepsis-induced cellular damage.
• The findings establish a comprehensive blood purification strategy for sepsis, highlighting the potential of PSQAE microspheres as a therapeutic agent.