Bridging Extracorporeal and Intracorporeal Approaches: A Blood Purification Strategy Using Biomimetic Magnetic Nanorobots for Timely Sepsis Therapy

Sepsis is a major global health burden with high incidence, mortality, and healthcare costs. In Hong Kong, it accounts for about one-quarter of adult deaths over the past decade. Current treatments focus on extracorporeal blood purification and intracorporeal micro/nano therapeutic systems, yet both face critical limitations. Extracorporeal devices require complex setups and bulky equipment that delay intervention, while micro/nano systems, though effective at clearing toxins, pose risks of long-term toxicity, off-target effects, and clinical translation challenges. Patient heterogeneity in inflammation and coagulation further complicates in vivo performance.This project bridges the advantages of extracorporeal purification and intracorporeal nanotherapy to create an innovative strategy for rapid detoxification and timely removal of nanomaterials in sepsis treatment. Biomimetic magnetic nanorobots, modified with blood cell membranes and specific peptides, are engineered with controlled ligand density and spatial organization to minimize steric hindrance and nonspecific binding.These nanorobots selectively capture bacterial toxins, pathogens, and inflammatory cytokines while maintaining excellent blood compatibility and immune evasion.Administered intravenously during early sepsis, they provide rapid systemic detoxification without the delay of extracorporeal setup. Binding specificity and efficiency will be validated in complex matrices under multi-target challenge conditions.⁠⁠⁠⁠⁠⁠⁠After detoxification, blood will circulate through an extracorporeal circuit integrating a portable magnetic separator. Within this device, nanorobots are captured as blood flows through parallel medical-grade PVC channels aligned above an NdFeB magnet array,forming localized high-gradient zones (∇B·B ≈ 10⁴–10⁵ T·m⁻¹). This configuration enables efficient nanoparticle capture under clinically acceptable flow and shear conditions, while viscosity and pump pressure are continuously monitored to prevent hemodynamic stress.Compared with traditional purification systems, the proposed platform enables faster response, greater flexibility, and simpler operation. Unlike conventional intracorporeal nanotherapies, it eliminates concerns about long-term nanoparticle retention and toxin redistribution through magnetically assisted retrieval. The system can be personalized to individual inflammatory and coagulation profiles and incorporates predefined immune monitoring for safety. Beyond sepsis, this versatile platform could be extended to other toxin-related diseases. The project also outlines a realistic roadmap for regulatory approval and clinical translation. Overall, this hybrid extracorporeal–intracorporeal strategy offers a promising new direction for sepsis management, with the potential to reduce disease severity, improve survival, and minimize complications of existing treatments.