Engineered　exosomes　have　become　popular　drug　delivery　carriers　for　cancer　treatment.　This　is　partially　due　to　the　interesting　property,　i.e.　exosome　organotropism,　which　plays　an　important　role　in　organ　distribution　post　systemic　administration.　Here,　we　demonstrated　that　breast　cancer　(MDA-MB-231)　cell-derived　exosomes　(231-Exo)　could　be　specifically　internalized　by　non-small　cell　lung　cancer　cells　via　a　specific　interaction　between　overexpressed　integrin　β4　(on　exosomes)　and　surfactant　protein　C　(SPC)　on　the　cancer　cells.　We　showed　that　231-Exo　was　capable　of　recognizing　A549　cells　in　blood　and　effectively　escaping　from　the　immune　surveillance　system　in　vitro.　Once　loaded　with　microRNA　molecules　in　the　exosome　carriers,　the　resulting,　miRNA-126　loaded　231-Exo　(miRNA-231-Exo)　strongly　suppressed　A549　lung　cancer　cell　proliferation　and　migration　through　the　interruption　of　the　PTEN/PI3K/AKT　signaling　pathway.　Intravenous　administration　of　the　miRNA-126　laden　exosomes　led　to　an　effective　lung　homing　effect　in　mice.　When　tested　in　a　lung　metastasis　model,　miRNA-231-Exo　resulted　in　an　efficacious　effect　in　inhibiting　the　formulation　of　lung　metastasis　in　vivo.　Collectively,　our　data　demonstrated　the　possibility　of　using　the　organotropism　feature　of　exosomes　in　exosome　carrier　design,　generating　a　potent　anti-metastasis　effect　in　a　mouse　model.　©　2019　The　Royal　Society　of　Chemistry.