As the foremost cause of cancer‐related death, metastasis consists of three steps: invasion, circulation, and colonization. Only targeting one single phase of the metastasis cascade may be insufficient since there are many alternative routes for tumor cells to disseminate. Here, to target the whole cascade of metastasis, hybrid erythrocyte and tumor cell membrane‐coated nanoparticle (Hyb‐NP) is designed with dual functions of increasing circulation time and recognizing primary, circulating, and colonized tumors. After loading with monensin, a recently reported metastasis inhibitor, the delivery system profoundly reduces spontaneous metastasis in an orthotopic breast cancer model. Underlying mechanism studies reveal that Hyb‐NP can deliver monensin to its action site in the Golgi apparatus, and in return, monensin can block the exocytosis of Hyb‐NP from the Golgi apparatus, forming a reservoir‐like subcellular structure. Notably, the Golgi apparatus reservoir displays three vital functions for suppressing metastasis initialization, including enhanced subcellular drug retention, metastasis‐related cytokine release inhibition, and directional migration inhibition. Collectively, based on metastasis cascade targeting at the tissue level, further formation of the Golgi apparatus drug reservoir at the subcellular level provides a potential therapeutic strategy for cancer metastasis suppression.

Cancer Metastasis Suppression In article number 2204747, Yuan Huang and co‐workers develop a strategy that enhances the targetability and retention of nano‐drug in Golgi apparatus (GA) for cancer metastasis suppression. Hybrid cell membrane‐coated nanoparticles cascade to delivering cargo into GA, and in return, loaded‐Monensin, an exocytosis inhibitor, blocks nano‐drug exocytosis like steel net. With GA retention of nano‐drug and GA dysfunction, this strategy suppresses metastasis initialization via multiple GA‐related pathways.