The prevention and treatment of lung metastasis of breast cancer remain a major challenge.The recent finding of vascular cell adhesion molecule-1 (VCAM-1) provides a potential therapeutic target in lung metastasis.Herein,succinobucol,a potent and selective VCAM-1 inhibitor,was entrapped into the nanoassembly of succinobucol and poloxamer 188 (P188) to improve the oral delivery and suppress the lung metastasis of breast cancer by inhibition of VCAM-1 expression.Succinobucol loaded in nanoassembly (SN) was nanometric particles with the mean diameter of 50.23±15.5 nm.The ceil migration and invasion abilities of 4T1 breast cancer cells was obviously inhibited by SN,but the cell viability was hardly reduced.The VCAM-1 expression on 4T1 cells was significantly reduced by SN,and the cell-cell binding ratio of RAW 264.7 cells to 4T1 cells obviously decreased from 47.4 %to 3.2%.Moreover,the oral bioavailability of succinobucol was greatly improved 13-fold by SN and the biodistribution in major organs was evidently enhanced.In particular,in the metastatic breast cancer model,the lung metastasis was notably reduced by SN treatment,and the VCAM-1 expression in lung tissues was significantly inhibited.Thereby,SN could evoke a novel effective therapeutic efficacy of succinobucol on lung metastasis of breast cancer by inhibition of VCAM-1 expression.