Self-assembled small messenger RNA nanospheres for efficient therapeutic apoptin expression and synergistic Gene-Chemotherapy of breast cancer.

Abstract In this work, small self-assembled messenger RNA nanospheres (mRNA-NSs) were successfully prepared by rolling circle transcription on a constructed apoptin plasmid. The self-assembled mRNA-NSs have a uniform diameter of approximately 65 nm, good dispersity in solution, and efficient therapeutic apoptin expression ability. In addition, the mRNA-NSs have a high loading capacity of 8.2% for the antitumor drug doxorubicin (Dox), which can effectively deliver the loaded Dox into 4 T1 cells. Cellular experiments show that Dox-loaded self-assembled messenger RNA nanospheres (mRNA-NSs@Dox) can reduce the viability of 4 T1 breast cancer cells by significantly upregulating Bax protein, thereby inducing the activation of Caspase 3 in 4 T1 cells. In vivo experiments show that mRNA-NSs@Dox can effectively increase the necrosis of tumor tissue, reduce the expression of Ki67, and exhibit a synergistic gene-chemotherapy effect in breast cancer-bearing mice. Taken together, this study successfully prepared self-assembled apoptin messenger RNA nanospheres (mRNA-NSs), which can improve the expression of the therapeutic protein apoptin and exhibit excellent synergistic antitumor effects after loading Dox, providing new ideas for the gene treatment and chemotherapy of breast cancer.