Charge-Engineered LPS-Targeting Magnetic Nano-adsorbents with Optimized Harvesting Strategy Advance Sepsis Blood Purification Nanotherapeutic

This study overcomes 2 critical barriers to the clinical translation of nano-adsorbents for sepsis blood purification: the weakening of adsorption function caused by nanoparticle biofouling and the limitations in clinical translation of recovery devices. We pioneer electrically neutral phosphocholine zwitterions as selective lipopolysaccharide (LPS) ligands. Their precise charge orientation resolves the core conflict between anti-fouling efficacy and LPS capture via differential dipole realignment upon LPS binding, enabling unprecedented selective LPS capture capacity with minimal protein adsorption. To address the persistent challenges of nano-adsorbent retrieval from blood, and clinical incompatibility of existing retrieval devices with blood purification systems, we developed a discretely assembled magnetic nanocomposite platform (PCAPAN-Fe) and an extracorporeal LPS-targeting magnetic array system (ELMAS), eliminating key risks inherent in monolithic designs while ensuring complete nanoparticle harvest. In septic rabbit models, the integrated platform exhibited 100% survival with early intervention, 84.7% LPS clearance (versus 20% survival and 45.6% LPS clearance for commercial adsorbents), and marked reduction of key proinflammatory cytokines. Crucially, the therapy achieved 82.2% LPS clearance efficacy in progressive sepsis, extending survival to 40% (versus 0% for commercial adsorbents). By ingeniously integrating molecular-level ligand design with a clinically viable device, this work pioneers a paradigm shifts in sepsis nanotherapeutic, resolving the performance-biosafety paradox in blood purification.