Abstract
Regular chemotherapy cannot eliminate leukemic cells, due to the sparse distribution of cancer cells in leukemia patients. Here, we report a precise nanostructure of folate-overhung mitoxantrone DNA tetrahedron that enables the treatment of leukemic cells by targeted action. Folate is used as a targeting molecule and synthesized with DNA strand in forming the folate-overhang DNA complement, and the complement is then separately base-paired onto six sides of the fabricated DNA tetrahedron. Mitoxantrone is used as an anticancer agent and intercalated into the double strands of the folate-overhung DNA tetrahedron for drug loading. The evaluation studies are performed on leukemia BALL-1 and K562 cells. The results demonstrate that the folate-overhung mitoxantrone DNA tetrahedra (approximately 25nm) are able to target leukemic cells, transport across the nuclei membrane, induce the apoptosis, and enhance the overall efficacy of treating leukemic cells in vitro and in leukemia-bearing mice. This study provides a potential drug-containing DNA nanostructure, to clean the sparsely distributed leukemic cells in patients.
Highlights
Based on Watson–Crick base paring, it is possible to generate immobile junctions or even three-dimensional DNA, rather than the linear duplexes on common occasions [1]
The native polyacrylamide gel electrophoresis (PAGE) analysis showed the step-wise assembly of DNA tetrahedra as each strand was added (Figure 1C)
The results demonstrate that the folate-overhung epirubicin DNA tetrahedron can be mostly captured by leukemic cells, and further delivered into the nuclei
Summary
Based on Watson–Crick base paring, it is possible to generate immobile junctions or even three-dimensional DNA, rather than the linear duplexes on common occasions [1]. DNA nanotechnology exhibits a promising prospect, because of its precise fabrication, stability, high biocompatibility and low immunogenicity [2]. It is proposed as an engineering material and a carrier of genetic information in living cells. Because of the sparse distribution of leukemic cells in the patients, current comprehensive treatments, including surgical, chemo-/radio, and bone marrow transplantation therapy, cannot eliminate leukemic cells. Chemotherapy plays a crucial role to sweep leukemic cells. Regular chemotherapy cannot eliminate the leukemic cells, due to the absence of specific capture capability
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