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A Precise Nanostructure of Folate-Overhung Mitoxantrone DNA Tetrahedron for Targeted Capture Leukemia
Ying-Zi Bu1, Jia-Rui Xu1, Qian Luo1
1State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
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 25 nm) 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.
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