Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells
Yanghao Zhou,1 Qiang Yang,1 Feng Wang,1 Zunjie Zhou,1 Jing Xu,1 Si Cheng,2 Yuan Cheng1 1Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of Orthopedics, The Second Affiliated Hospital of C...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/2bdc8a7f10074ad7b0f39672c43b74a4 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:2bdc8a7f10074ad7b0f39672c43b74a4 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:2bdc8a7f10074ad7b0f39672c43b74a42021-12-02T13:26:18ZSelf-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells1178-2013https://doaj.org/article/2bdc8a7f10074ad7b0f39672c43b74a42021-03-01T00:00:00Zhttps://www.dovepress.com/self-assemblednbspdna-nanostructure-as-a-carrier-for-targeted-sirna-de-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yanghao Zhou,1 Qiang Yang,1 Feng Wang,1 Zunjie Zhou,1 Jing Xu,1 Si Cheng,2 Yuan Cheng1 1Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Yuan ChengDepartment of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaEmail chengyuan@hospital.cqmu.edu.cnSi ChengDepartment of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaEmail 304238@cqmu.edu.cnIntroduction: RNA interference is a promising therapy in glioma treatment. However, the application of RNA interference has been limited in glioma therapy by RNA instability and the lack of tumor targeting. Here, we report a novel DNA tetrahedron, which can effectively deliver small interfering RNA to glioma cells and induce apoptosis.Methods: siRNA, a small interfering RNA that can suppress the expression of survivin in glioma, was loaded into the DNA tetrahedron (TDN). To enhance the ability of active targeting of this nanoparticle, we modified one side of the DNA nanostructure with aptamer as1411 (As-TDN-R), which can selectively recognize the nucleolin in the cytomembrane of tumor cells. The modified nanoparticles were characterized by agarose gel electrophoresis, dynamic light scattering, and transmission electron microscopy. The serum stability was evaluated by agarose gel electrophoresis. Nucleolin was detected by Western blot and immunofluorescence, and targeted cellular uptake was examined by flow cytometry. The TUNEL assay, flow cytometry, and Western Blot were used to detect apoptosis in U87 cells. The gene silencing of survivin was examined by qPCR, Western Blot, and immunofluorescence.Results: As-TDN-R alone showed better stability towards siRNA, indicating that TDN was a good siRNA protector. Compared with TDN alone, there was increased intercellular uptake of As-TDN-R by U87 cells, evidenced by overexpressed nucleolin in glioma cell lines. TUNEL assay, flow cytometry, and Western Blot revealed increased apoptosis in the As-TDN-R group. The downregulation of survivin protein and mRNA expression levels indicated that As-TDN-R effectively silenced the target gene.Conclusion: The novel nanoparticle can serve as a good carrier for targeting siRNA delivery in glioma. Further exploration of the DNA nanostructure can greatly promote the application of DNA-based drug systems in glioma.Keywords: DNA tetrahedron, nanomedicine, tumor targeting, aptamer, apoptosis, RNA interferenceZhou YYang QWang FZhou ZXu JCheng SCheng YDove Medical Pressarticledna tetrahedronnanomedicinetumor targetingaptamerapoptosisrna interferenceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1805-1817 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
dna tetrahedron nanomedicine tumor targeting aptamer apoptosis rna interference Medicine (General) R5-920 |
| spellingShingle |
dna tetrahedron nanomedicine tumor targeting aptamer apoptosis rna interference Medicine (General) R5-920 Zhou Y Yang Q Wang F Zhou Z Xu J Cheng S Cheng Y Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells |
| description |
Yanghao Zhou,1 Qiang Yang,1 Feng Wang,1 Zunjie Zhou,1 Jing Xu,1 Si Cheng,2 Yuan Cheng1 1Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Yuan ChengDepartment of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaEmail chengyuan@hospital.cqmu.edu.cnSi ChengDepartment of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaEmail 304238@cqmu.edu.cnIntroduction: RNA interference is a promising therapy in glioma treatment. However, the application of RNA interference has been limited in glioma therapy by RNA instability and the lack of tumor targeting. Here, we report a novel DNA tetrahedron, which can effectively deliver small interfering RNA to glioma cells and induce apoptosis.Methods: siRNA, a small interfering RNA that can suppress the expression of survivin in glioma, was loaded into the DNA tetrahedron (TDN). To enhance the ability of active targeting of this nanoparticle, we modified one side of the DNA nanostructure with aptamer as1411 (As-TDN-R), which can selectively recognize the nucleolin in the cytomembrane of tumor cells. The modified nanoparticles were characterized by agarose gel electrophoresis, dynamic light scattering, and transmission electron microscopy. The serum stability was evaluated by agarose gel electrophoresis. Nucleolin was detected by Western blot and immunofluorescence, and targeted cellular uptake was examined by flow cytometry. The TUNEL assay, flow cytometry, and Western Blot were used to detect apoptosis in U87 cells. The gene silencing of survivin was examined by qPCR, Western Blot, and immunofluorescence.Results: As-TDN-R alone showed better stability towards siRNA, indicating that TDN was a good siRNA protector. Compared with TDN alone, there was increased intercellular uptake of As-TDN-R by U87 cells, evidenced by overexpressed nucleolin in glioma cell lines. TUNEL assay, flow cytometry, and Western Blot revealed increased apoptosis in the As-TDN-R group. The downregulation of survivin protein and mRNA expression levels indicated that As-TDN-R effectively silenced the target gene.Conclusion: The novel nanoparticle can serve as a good carrier for targeting siRNA delivery in glioma. Further exploration of the DNA nanostructure can greatly promote the application of DNA-based drug systems in glioma.Keywords: DNA tetrahedron, nanomedicine, tumor targeting, aptamer, apoptosis, RNA interference |
| format |
article |
| author |
Zhou Y Yang Q Wang F Zhou Z Xu J Cheng S Cheng Y |
| author_facet |
Zhou Y Yang Q Wang F Zhou Z Xu J Cheng S Cheng Y |
| author_sort |
Zhou Y |
| title |
Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells |
| title_short |
Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells |
| title_full |
Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells |
| title_fullStr |
Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells |
| title_full_unstemmed |
Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells |
| title_sort |
self-assembled dna nanostructure as a carrier for targeted sirna delivery in glioma cells |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/2bdc8a7f10074ad7b0f39672c43b74a4 |
| work_keys_str_mv |
AT zhouy selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells AT yangq selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells AT wangf selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells AT zhouz selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells AT xuj selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells AT chengs selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells AT chengy selfassemblednbspdnananostructureasacarrierfortargetedsirnadeliveryingliomacells |
| _version_ |
1718393019922644992 |