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Tumor-Penetrating Peptide-Modified DNA Tetrahedron for Targeting Drug Delivery

作者:Zhiwei Xia, Ping Wang, Xunwei Liu, Ting Liu, Yinan Yan, Juan Yan, Jian Zhong, Gang Sun, Dannong He · 发表于:Biochemistry · 年份:2016 · DOI:10.1021/acs.biochem.5b01181 · 被引用次数:153 · 研究领域:Advanced biosensing and bioanalysis techniques、RNA Interference and Gene Delivery、DNA and Nucleic Acid Chemistry

DNA self-assembling nanostructure has been considered as a promising candidate as a drug delivery vehicle because of its compactness, mechanical stability, and noncytotoxicity. In this work, we developed functional, multiform DNA nanostructures by appending a tumor-penetrating peptide to tetrahedral DNA nanostructure (p-TDN). This functional structure is able to efficiently increase the rate of uptake of glioblastoma cell U87MG compared with the DNA tetrahedron and the double-stranded DNA structures. We found that the DNA tetrahedron plays the main role in the endocytosis of U87MG cells, whereas the tumor-penetrating peptide could also bind to transmembrane glycoprotein neuropilin-1 and mediate the endocytosis of the p-TDN nanostructure. Moreover, given the high efficiency of the growth inhibitory effect of the p-TDN loading doxorubicin hydrochloride, the p-TDN distinguishes itself as a promising candidate as an effective delivery carrier.