Visualizing and Targeting Tumor-Associated Neutrophils: Advanced Imaging, Therapeutic Reprogramming, and Cell-Based Delivery for Precision Oncology.

Tumor-associated neutrophils (TANs) are increasingly recognized as heterogeneous and context-dependent regulators of cancer progression and treatment response. Through cytokine secretion, protease release, oxidative activity, and formation of neutrophil extracellular traps (NETs), TANs remodel the tumor microenvironment (TME) and influence immune regulation, angiogenesis, invasion, and metastasis. Recent advances in molecular imaging enable selected neutrophil-associated molecular processes to be monitored in vivo using optical, photoacoustic, chemiluminescent, and magnetic resonance approaches. These approaches include neutrophil elastase (NE) activity-responsive imaging, NETosis-related imaging, and myeloperoxidase (MPO) activity-responsive imaging. These readouts provide spatially and temporally resolved information on neutrophil-associated molecular activity and, when combined with complementary cellular, histological, and functional analyses, support more robust characterization of the underlying cellular sources and biological functions. In parallel, neutrophil-directed treatments seek to limit recruitment, suppress or reprogram protumor functions, and inhibit NET formation or promote NET clearance. Neutrophils and neutrophil-derived materials are also being developed as drug-delivery platforms, including live or engineered neutrophils, neutrophil membrane-coated nanocarriers, and extracellular vesicles. This review summarizes advances across these areas and discusses how imaging readouts relate to biological interpretation, candidate interventions, confirmatory assessments, therapeutic outcomes, and safety. Although current evidence remains predominantly preclinical and context dependent, integrating molecular imaging with cellular phenotyping, functional validation, and longitudinal outcome assessment may support more selective and adaptive neutrophil-centered strategies for precision oncology.