Extracorporeal Catalytic Hemoperfusion Therapy for Refractory Septic Shock Using Ceria Nanoparticle-Embedded Porous Microbeads

Abstract

Septic shock is a life-threatening medical condition characterized by organ dysfunction resulting from a dysregulated host response to infection and marked by rapid, ubiquitous generation of reactive oxygen species (ROS). Although extracorporeal devices can remove pathogenic endotoxins or inflammatory cytokines, it is not yet possible to effectively target the excessive ROS in the blood of patients with sepsis. Here, a novel extracorporeal blood purification system is proposed based on porous microbeads embedded with autocatalytic ceria nanoparticles (CeNPs), as a safer and potentially life-saving solution for septic shock. Porous microbeads (PMB), consisting of an assembly of mesoporous silica particles, are loaded with a large amount of CeNPs and subsequently coated with polyvinylpyrrolidone, a hydrophilic and blood-compatible polymer (P-Ce-PMB). A hemoperfusion column cartridge composed of P-Ce-PMB exhibited effective and durable ROS-scavenging capability and hemocompatibility, without inducing blood clotting during perfusion. Further, in a refractory septic shock animal model, hemoperfusion through such a cartridge has a 100% survival rate compared to 0% in the standard intensive care group, accompanied by significant improvements in hemodynamic profiles and multiple organ injuries. This study highlights the potential of effective ROS-scavenging in extracorporeal hemoperfusion as a viable clinical strategy for septic shock therapy.