An antigen/chemotherapy co-loaded DNA nanocube inserts into tumor cell plasma membrane and enhances chemo-and immunotherapy

Abstract

Breast cancer is the most frequently diagnosed female cancer. Combined chemo- and immunotherapies have been extensively explored to treat breast cancer. To improve the efficacy of the combined therapies, this study designed a hollow DNA nanocube with four cholesterol anchors (C2.2) that could be inserted into breast cancer cell plasma membrane. A model antigen-ovalbumin (OVA₂₅₇-₂₆₄) was further conjugated to C2.2 to construct C2.2-OVA and a model chemotherapy-Doxorubicin (DOX) was also loaded to C2.2-OVA to prepare DOX@C2.2-OVA for the combined chemo- and immunotherapy to treat breast cancer. C2.2, C2.2-OVA, and DOX@C2.2-OVA were successfully prepared and possessed square-like shape and small size. C2.2 and C2.2-OVA could be anchored in breast cancer cell plasma membrane for at least 10 h. C2.2-OVA demonstrated the significantly higher activation rates of DC cells than free OVA. Although C2.2 showed no cytotoxicity, C2.2 increased the potency of 5-FU and carboplatin to MCF-7 and 4 T1 breast cancer cells. DOX@C2.2-OVA treatment to 4 T1 tumor in vivo showed the significant reduction of tumor size and weight, and resulted in more DCs and CD8⁺ T cells in 4 T1 tumor. In summary, DOX@C2.2-OVA that could be inserted into tumor cell plasma membrane enhanced the combined chemo- and immunotherapy for the breast cancer treatment.