Complement-Opsonized NIR-IIb Emissive Immunotracers for Dynamically Monitoring Neutrophils in Inflammation-Related Diseases

Real-time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation-related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeling the cells. Inspired by the natural biological function of the complement system, a strategy of enhancing the complement C3 opsonization of lanthanide-doped nanoparticles (LnNPs) by modulating their surface chemistry, thus developing a near infrared-IIb emissive nanotracer for neutrophils, is reported herein. Four kinds of surface-modified LnNPs are fabricated, among which phospholipids DOPG-modified LnNPs (LnNPs@PG) with weak antifouling ability and hydroxyl groups adsorb more complement C3 proteins and form covalent linkages with C3b active fragments under inflammation conditions, inducing enhanced complement C3 opsonization. Therefore, LnNPs@PG with enhanced complement C3 opsonization are capable of efficiently labeling inflammation-stimulated neutrophils in vivo through complement-receptors-mediated phagocytosis and achieve dynamic monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion.

Automated summary

This study reports a strategy of enhancing the complement C3 opsonization of lanthanide-doped nanoparticles (LnNPs) by modulating their surface chemistry, leading to the development of a near infrared-IIb emissive nanotracer for neutrophils. The nanotracer efficiently labels inflammation-stimulated neutrophils and enables real-time monitoring of neutrophil dynamics during wound healing and cerebral ischemia/reperfusion.