Neutrophils: Heterogeneity, Biology, Diseases, and Therapeutic Strategies

Neutrophils are the most abundant circulating leukocytes and are essential components of innate immunity, contributing to host defense, inflammation, tissue remodeling, and disease progression. Increasing evidence has revealed substantial neutrophil heterogeneity and functional plasticity, which enable distinct neutrophil populations to exert protective or pathogenic effects depending on the tissue and disease context. These properties have attracted growing interest in neutrophils as therapeutic targets and as vehicles for targeted drug delivery. This review summarizes the biological characteristics and functional heterogeneity of neutrophils, with particular emphasis on their recruitment, phagocytosis, oxidative responses, extracellular trap formation, and interactions with the tissue microenvironment. We further discuss the diverse roles of neutrophils in cancer, inflammatory diseases, infectious diseases, and other pathological conditions, highlighting their context-dependent functions. Building on these insights, we review current and emerging therapeutic strategies, ranging from broad neutrophil modulation to precision targeting and neutrophil-based drug delivery. Living neutrophil carriers, neutrophil membrane-coated nanoparticles, and neutrophil-derived vesicles are comparatively evaluated in terms of preparation, cargo loading, targeting properties, advantages, limitations, and translational potential. Finally, we discuss key challenges in the development and clinical translation of neutrophil-based therapies, including manufacturing, quality control, safety, and therapeutic precision, and highlight future opportunities for their clinical application.