A Precise Nanostructure of Folate-Overhung Mitoxantrone DNA Tetrahedron for Targeted Capture Leukemia

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.

Recent Advances of DNA Tetrahedra for Therapeutic Delivery and Biosensing

“…Reproduced with permission from ref. [34]; published: 2020 by MDPI under Creative Commons licence 4.0. D) Reducible disulfide bridges on the DNA backbone target mouse tumours with a generic hydrophobic drug.…”

“…This problem was addressed by Bu et al. who combined the targeting effects of folate and the anticancer properties of mitoxantrone with the excellent nuclease stability and cellular internalization of TDNs [34] . Interestingly, their TDN was assembled by 6 oligonucleotides with folate overhangs producing a mixture of products (0–6 folate residues).…”

A nanocarrier system based on CQDs for efficient mitoxantrone drug delivery

“…This drug mainly acts on DNA, causing a break in DNA strands by stabilizing the cleavable DNA-topoisomerase complex and producing free radicals. Moreover it causes DNA accumulation and condensation through electrostatic cross-linking [ 7 ]. MTX drug has also been used as one of the most effective agents for the treatment of relapsing-remitting, progressive-relapsing, and secondary progressive multiple sclerosis by slowing down the worsening of neurological disability [ 8 ].…”

Targeting nano-regulator based on metal–organic frameworks for enhanced immunotherapy of bone metastatic prostate cancer

“…The MOF structure not only served as a facile payload for drug encapsulation with high loading capacity (30%), but also provided an intrinsic targeting property towards metastatic bone tumors by virtue of enhanced permeability and retention (EPR) effect of tumor and high affinity of PA towards bone tissue (Zhou et al 2019). Upon targeting delivery, the released MTO as an anti-tumor drug could directly inhibit tumor growth, and induce tumor cells immunogenic cell death (ICD) to promote anti-tumor immunity (Bu et al 2020). Moreover, MTO bound the receptor of TGF-β on various immune cells surface to induce its degradation, thus abolishing the function of TGF-β.…”