Abstract

Metastatic cancer progression is critically driven by intercellular communication networks that enable tumor 
cells to remodel distant microenvironments, evade immune surveillance, and acquire invasive phenotypes. 
Among the most influential mediators of this communication are exosomes nanoscale extracellular vesicles that 
transfer proteins, lipids, and nucleic acids between cells. Tumor-derived exosomes actively orchestrate pre
metastatic niche formation, promote epithelial–mesenchymal transition, and reprogram stromal and immune 
cells to support dissemination. However, directly targeting endogenous exosomes remains technically 
challenging due to their heterogeneity, abundance, and physiological roles. Exosome-mimetic nanoparticles 
have emerged as a powerful alternative, designed to structurally and functionally resemble natural exosomes 
while offering superior controllability, scalability, and engineering flexibility. These biomimetic systems can 
competitively intercept pathological signaling, sequester oncogenic cargo, or deliver therapeutic agents that 
disrupt metastatic communication pathways. This review provides a comprehensive analysis of exosome
mimetic nanoparticles as tools for intercellular signal interception in metastatic cancer. We examine their design 
principles, mechanisms of action, and applications in blocking tumor–stromal, tumor–immune, and tumor
tumor communication. Preclinical progress, translational challenges, and future directions toward clinical 
implementation are critically discussed, highlighting their promise in next-generation anti-metastatic therapies. 
Keywords: exosome-mimetic nanoparticles; metastatic cancer; intercellular communication; signal interception;