Dual ATP/reduction-responsive polyplex to achieve the co-delivery of doxorubicin and miR-23b for the cancer treatment

Combination therapy based on the co-delivery of therapeutic genes and anti-cancer drugs has emerged as a promising approach in the cancer treatment, and stimuli-responsive delivery systems could further improve the therapeutic efficacy. Herein, an ATP aptamer and its complementary DNA were used to form Duplex into which doxorubicin (DOX) was loaded to construct DOX-Duplex, and then the lipoic acid-modified oligoethyleneimine (LA-OEI) was employed as a carrier to realize the co-delivery of DOX-Duplex and miR-23b. The ternary nano complex LA-OEI/miR-23b/DOX-Duplex showed excellent anti-proliferative effect by inducing the cell apoptosis via mitochondrial signaling pathway and arresting the cell cycle at S phase. Meanwhile, the co-delivery of DOXDuplex and miR-23b could efficiently inhibit the metastasis of cancer cells by reducing the expression level of MMP-9. The favorable anti-tumor efficacy of ternary nanocomplex was attributed to the rapid drug release in response to intracellular ATP concentration and reduction conditions and the synergistic effect between DOXDuplex and miR-23b. Thus, ATP aptamer and reduction-responsive polymer provided a convenient platform to construct dual stimuli-responsive systems for the co-delivery of gene and drug in the cancer treatment.