Programmed nanocarrier loaded with paclitaxel and dual-siRNA to reverse chemoresistance by synergistic therapy

Paclitaxel (PTX) is commonly used in clinical tumor therapy. However, chemoresistance and the inducement of tumor metastasis severely affect the efficacy of PTX. To develop a treatment strategy to reverse chemoresistance, the co-delivery of PTX and small interfering RNA with nanocarriers were programmed in this study. The carrier we have programmed exhibits excellent safety, stability, and delivery efficiency for co-delivery of siRNA and PTX. After rapid release of siRNA, PTX could be released within 72 h. The siBcl-xL and siMcl-1 inhibited cell migration decreased the mitochondrial membrane potential, and induced the release of reactive oxygen species while synergistically functioning with the antineoplastic effects of PTX. Our strategy reduced IC50 values by 2-5fold in different cell lines, and the results of flow cytometry confirmed increased apoptosis rates and effectively inhibited cell migration. Synergistic therapy effectively reversed chemoresistance in PTX-resistant breast cancer cells. Similarly, the synergistic administration strategy showed significant sensitizing effects in vivo. Our study demonstrates the combined application of multiple synergistic antitumor administration strategies.