Theranostic Toolbox for Neutrophil Functionalization

Neutrophils are crucial for fighting invading pathogens and for the clearance of sterile wounds. However, in cases of overwhelming pathogens or excessive inflammatory responses, fine-tuning of neutrophil functions can help to either enhance bacterial killing or prevent unwanted tissue damage. Thus, the present study is aimed at developing a nanoparticle-based toolbox to direct neutrophils toward either a proinflammatory or reparative phenotype tailored to the specific inflammatory environment. For this, neutrophil-specific fluorine nanoparticles additionally equipped with either activating or inhibiting peptides for a background-free ¹⁹F MRI-based theranostic approach are engineered. It is demonstrated that with this i) distinct effector functions can be specifically modulated in both murine and human neutrophils, ii) the disease-specific degree of neutrophil infiltration can be non-invasively monitored in vivo, and in turn iii) neutrophil effector functions can either be attenuated during a pharmacological challenge or amplified to ameliorate tissue damage during bacteria-driven acute colitis. Thus, this nanotheranostic approach is suitable to visualize and concomitantly direct neutrophil functionality depending on the specific requirements to improve disease course and outcome, thus paving the way for a personalized neutrophil immunotherapy.