Turning Foe into Friend: Bridging Neutrophil Biological Characteristics and Neutrophil‐Based Oncolytic Nanotherapeutics

Abstract Neutrophils, the primary responders to inflammation in infection and cancer, exhibit precise chemotaxis to target sites. They also show functional plasticity in tumor progression, with distinct subsets exerting opposing effects—either fostering oncogenesis or mediating antitumor responses. Recently, the introduction of nanotherapeutics offers the opportunity to effectively augment the anti‐tumor effects of neutrophils and avoid the risk of tumor promotion during treatment. In this review, oncopromotion (cell proliferation, angiogenesis, immunodepression, and DNA injury), a combination of oncogenesis and promotion, and metastasis (transmigration and pre‐niche) conditions are used to summarize the tumorigenic effect of neutrophils. Regarding the tumor suppression mechanism of neutrophils, three “C” stages are further generalized that is, coordination, cytolysis, and chemosecretion. Neutrophils coordinate innate and adaptive immunity via cytokines and surface molecules, mediate antibody‐dependent cytotoxicity to disrupt cancer cell membranes, and secrete inflammatory factors to modulate ion channels and directly kill tumor cells. Capitalizing on neutrophils' chemotaxis and nanotherapeutic interactions, membrane encapsulation and whole‐cell mediation nanoplatforms are integrated to synthesize cutting‐edge advancements in neutrophil nanomedicines, particularly, multimechanistic anticancer strategies. Last but not least, an outlook for introducing AI aimed at improving the safety, scalability, and reproducibility of neutrophil‐based oncolytic nanotherapeutics is provided.