Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence
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 f...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383521000472 |
| _version_ | 1818930160381984768 |
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| author | Xiu Han Xiang Xu Ziheng Wu Zhenghong Wu Xiaole Qi |
| author_facet | Xiu Han Xiang Xu Ziheng Wu Zhenghong Wu Xiaole Qi |
| author_sort | Xiu Han |
| collection | DOAJ |
| description | 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, a+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. |
| first_indexed | 2024-12-20T03:56:17Z |
| format | Article |
| id | doaj.art-a187af7183d243e2a5b7a97434463c99 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-20T03:56:17Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-a187af7183d243e2a5b7a97434463c992022-12-21T19:54:19ZengElsevierActa Pharmaceutica Sinica B2211-38352021-10-01111032863296Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silenceXiu Han0Xiang Xu1Ziheng Wu2Zhenghong Wu3Xiaole Qi4Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China; Medical School of Nanjing University, Nanjing University, Nanjing 210093, ChinaKey Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, ChinaParkville Campus, Monash University, VIC 3052, AustraliaKey Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors.Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors.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, a+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.http://www.sciencedirect.com/science/article/pii/S2211383521000472i-motifsiRNAGene deliveryDNA tetrahedronEndosomal escapeCancer |
| spellingShingle | Xiu Han Xiang Xu Ziheng Wu Zhenghong Wu Xiaole Qi Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence Acta Pharmaceutica Sinica B i-motif siRNA Gene delivery DNA tetrahedron Endosomal escape Cancer |
| title | Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence |
| title_full | Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence |
| title_fullStr | Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence |
| title_full_unstemmed | Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence |
| title_short | Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence |
| title_sort | synchronous conjugation of i motif dna and therapeutic sirna on the vertexes of tetrahedral dna nanocages for efficient gene silence |
| topic | i-motif siRNA Gene delivery DNA tetrahedron Endosomal escape Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211383521000472 |
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