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

Pre-metastatic 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 pre-metastatic 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 were converted into dead neutrophils ( C NE) through a quick-frozen process to maintain PMN-targeting and tumor-derived secreted factor-consuming abilities but eliminate NET-releasing shortcoming. Considering macrophages-regulated remodeling of the extracellular matrix in PMN, bacterial magnetosomes (Mag) were further hitchhiked on the surface of C NE to form C NE Mag , which could 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 C NE Mag in suppression of PMN formation and metastasis. This study presents a promising strategy for targeted anti-metastatic therapy in clinics. This article is protected by copyright. All rights reserved.