期刊
ACTA PHARMACEUTICA SINICA B
卷 11, 期 10, 页码 3286-3296出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2021.02.009
关键词
i-motif; siRNA; Gene delivery; DNA tetrahedron; Endosomal escape; Cancer; Gene silence; Biocompatibility
资金
- Double First-Class Innovation Team of China Pharmaceutical University (China) [CPU2018GY40]
- National Mega-project for Innovative Drugs (China) [2019ZX09721001]
DNA tetrahedron nanocages conjugated with i-motif showed good endosomal escape behaviors in tumor cells, downregulating the expression of epidermal growth factor receptor. In tumor-bearing mice, the treatment with 2X-Td@2siRNA significantly inhibited tumor growth compared to non-i-motif-conjugated Td@2siRNA and free siRNA. These results demonstrate a general strategy for achieving effective in vivo gene delivery and therapy with DNA nanostructures.
The functionality of DNA biomacromolecules has been widely excavated, as therapeutic drugs, carriers, and functionalized modification derivatives. In this study, we developed a series of DNA tetrahedron nanocages (Td), via synchronous conjugating different numbers of i-(X) and therapeutic siRNA on four vertexes of tetrahedral DNA nanocage (aX-Td@bsiRNA, at+b = 4). This i-motif-conjugated Td exhibited good endosomal escape behaviours in A549 tumor cells, and the escape efficiency was affected by the number of i-motif. Furthermore, the downregulating mRNA and protein expression level of epidermal growth factor receptor (EGFR) caused by this siRNA embedded Td were verified in A549 cells. The tumor growth inhibition efficiency of the 2X-Td@2siRNA treated group in tumor-bearing mice was significantly higher than that of non-i-motif-conjugated Td@2siRNA (3.14-fold) and free siRNA (3.63-fold). These results demonstrate a general strategy for endowing DNA nanostructures with endosomal escape behaviours to achieve effective in vivo gene delivery and therapy. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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