Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis.

High recurrence and metastasis of triple-negative breast cancer (TNBC) after operation is a leading cause of breast cancer related death. The pre-metastatic niche (PMN) is an environment in a secondary organ conducive to the metastasis of a primary tumor. Herein, we identify exosomes from autologous breast cancer cells that show effective lung targeting ability. Based on this, we developed the biomimetic nanoparticles (cationic bovine serum albumin (CBSA) conjugated siS100A4 and exosome membrane coated nanoparticles, CBSA/siS100A4@Exosome) to improve drug delivery to the lung PMN. CBSA/siS100A4@Exosome self-assembled nanoparticles formed homogeneous sizes of ~200 nm, protected siRNA from degradation, and showed excellent biocompatibility. Further in vivo studies showed that CBSA/siS100A4@Exosome had a higher affinity toward lung in comparison to the CBSA/siS100A4@Liposome, and exhibited outstanding gene-silencing effects that significantly inhibited the growth of malignant breast cancer cells. Taken together, these results indicate that CBSA/siS100A4@Exosome self-assembled nanoparticles are a promising strategy to suppress postoperative breast cancer metastasis.