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Mitochondrial-targeted tetrahedral DNA nanostructures for doxorubicin delivery and enhancement of apoptosis

Abstract

Mitochondria-targeted nanoparticles such as liposomes, polymers and inorganic particles suffer from heterogeneity, low biocompatibility and low drug loading efficiency. Here, we presented a novel delivery platform based on tetrahedral DNA nanostructures (TDNs) that enables mitochondria transportation of anticancer drug doxorubicin (DOX) for cancer therapy. In our design, DOX was intercalated into TDNs, which executed the cell-killing function inside the tumor cells. Various number of D-(KLAKLAK)2 were conjugated to TDNs to achieve mitochondria targeting effect. The mean size of KLA modified TDNs was about 15 nm and the TDNs were stable in FBS. The DOX loading efficiency of TDNs was up to around 77%. 3KLA modified TDNs exhibited the most efficient DOX accumulation in mitochondria, leading to effective release of cytochrome c, the raised expression level of caspase-9, caspase-3, p21 and p53. Meanwhile, 3KLA-TDNs/DOX elevated the pro-apoptotic Bax, reduced the anti-apoptotic Bcl-2 protein expression and increased Bax/Bcl-2 ratio, which finally activated the mitochondria-mediated programmed apoptosis pathway to enhance anticancer efficacy in vitro. This 3KLA-TDNs and DOX co-assembling strategy can be further developed to transport other anthracyclines and chemotherapeutic agents for enhanced apoptosis effect.

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Publication details

The article was received on 14 Oct 2019, accepted on 25 Nov 2019 and first published on 27 Nov 2019


Article type: Paper
DOI: 10.1039/C9TB02266J
J. Mater. Chem. B, 2019, Accepted Manuscript

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    Mitochondrial-targeted tetrahedral DNA nanostructures for doxorubicin delivery and enhancement of apoptosis

    J. Yan, J. Chen, N. Zhang, Y. Yang, W. Zhu, L. Li and B. He, J. Mater. Chem. B, 2019, Accepted Manuscript , DOI: 10.1039/C9TB02266J

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