Bacterial Magnetosome‐Hitchhiked Quick‐Frozen Neutrophils for Targeted Destruction of Pre‐Metastatic Niche and Prevention of Tumor Metastasis

Abstract

Premetastatic niche (PMN) is a prerequisite for tumor metastasis. Destruction of PMN can significantly suppress the tumor metastasis. Bone marrow‐derived cells are usually recruited into the premetastatic organs to support PMN formation, which can be orchestrated by tumor‐derived secreted factors. Neutrophils can chemotactically migrate towards the inflammatory sites and consume tumor‐derived secreted factors, capable of acting as therapeutic agents for a broad‐spectrum suppression of PMN formation and metastasis. However, neutrophils in response to inflammatory signals can release neutrophil extracellular traps (NETs), promoting the tumor metastasis. Herein, live neutrophils are converted into dead neutrophils (_CNE) through a quick‐frozen process to maintain PMN‐targeting and tumor‐derived secreted factor‐consuming abilities but eliminate NET‐releasing shortcomings. Considering macrophages‐regulated remodeling of the extracellular matrix in PMN, bacterial magnetosomes (Mag) are further hitchhiked on the surface of _CNE to form _CNE^Mag, which can repolarize macrophages from M2 to M1 phenotype for further disruption of PMN formation. A series of in vitro and in vivo assessments have been applied to confirm the effectiveness of _CNE^Mag in suppression of PMN formation and metastasis. This study presents a promising strategy for targeted anti‐metastatic therapy in clinics.