Macrophage-red blood cell hybrid membrane-coated ultrasound-responsive microbowls to eliminate pathogens, endotoxins, and heavy metal ions from blood

Abstract

Sepsis is a potentially life-threatening condition triggered by pathogens such as bacteria and toxins. In clinical settings, hemoperfusion has been used as a therapeutic technique for the treatment of sepsis to remove pathogens, toxins and other inflammatory mediators from the bloodstream. However, the existing adsorption process of hemoperfusion is not specific to sepsis-related pathogens or toxins, resulting in unsatisfactory removal effectiveness and the lack of capture selectivity. Herein, we developed an ultrasound-responsive asymmetric polymeric microbowl coated with macrophage and red blood cell (RBC) membranes to selectively eliminate pathogens, toxins, and heavy metal ions from blood. Poly(glycidyl methacrylate) spherical microparticles were first synthesized and then eroded using dibutyl phthalate and styrene to form a microbowl structure. This asymmetric structure could provide acoustic radiation pressure gradients to realize orientation motion under non-invasive ultrasound fields with a velocity of 37.14 μm s⁻¹ at 20 V_p–p, which could increase adsorption efficiency in physiological environments by fuel-free programable movements. In addition, the macrophage and RBC membrane coating endowed the microbowl with desired biocompatibility, enhanced blood circulation and the ability to selectively eliminate endotoxins, bacteria and heavy metal ions. Endotoxin removal assay showed that 92.80% of endotoxin was eliminated within 15 minutes. Owing to the affinity between the red blood cell membrane and heavy metal ions, the removal efficiency reached 92.75% and 93.91% for Pb²⁺ and Hg²⁺, respectively. Meanwhile, over 90% of S. aureus in the blood was eliminated owing to the selective recognition and adhesion of bacteria by macrophage membrane proteins. Overall, this work on ultrasound-responsive asymmetric polymeric microbowls provides a new insight to eliminate pathogens, toxins and heavy metal ions from the bloodstream for sepsis treatment.