Nano-Structural Effects on Gene Transfection: Large, Botryoid-Shaped Nanoparticles Enhance DNA Delivery via Macropinocytosis and Effective Dissociation
文献类型：期刊论文
| 作者 | Zhang, Wenyuan1,2; Kang, Xuejia1,3; Yuan, Bo4; Wang, Huiyuan1 ; Zhang, Tao1; Shi, Mingjie1; Zheng, Zening1,3; Zhang, Yuanheng1; Peng, Chengyuan1; Fan, Xiaoming1
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| 刊名 | THERANOSTICS
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| 出版日期 | 2019 |
| 卷号 | 9期号:6页码:1580-1598 |
| 关键词 | gene delivery PEI micropinocytosis TRAIL local-regional gene therapy cervical cancer |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.30302 |
| 通讯作者 | Huang, Yongzhuo(yzhuang@simm.ac.cn) |
| 英文摘要 | Effective delivery is the primary barrier against the clinical translation of gene therapy. Yet there remains too much unknown in the gene delivery mechanisms, even for the most investigated polymeric carrier (i.e., PEI). As a consequence, the conflicting results have been often seen in the literature due to the large variability in the experimental conditions and operations. Therefore, some key parameters should be identified and thus strictly controlled in the formulation process. Methods: The effect of the formulation processing parameters (e.g., concentration or mixture volume) and the resulting nanostructure properties on gene transfection have been rarely investigated. Two types of the PEI/DNA nanoparticles (NPs) were prepared in the same manner with the same dose but at different concentrations. The microstructure of the NPs and the transfection mechanisms were investigated through various microscopic methods. The therapeutic efficacy of the NPs was demonstrated in the cervical subcutaneous xenograft and peritoneal metastasis mouse models. Results: The high-concentration process (i.e., small reaction-volume) for mixture resulted in the large-sized PEI/DNA NPs that had a higher efficiency of gene transfection, compared to the small counterpart that was prepared at a low concentration. The microstructural experiments showed that the prepared small NPs were firmly condensed, whereas the large NPs were bulky and botryoid-shaped. The large NPs entered the tumor cells via the macropinocytosis pathway, and then efficiently dissociated in the cytoplasm and released DNA, thus promoting the intranuclear delivery. The enhanced in vivo therapeutic efficacy of the large NPs was demonstrated, indicating the promise for local-regional administration. Conclusion: This work provides better understanding of the effect of formulation process on nano-structural properties and gene transfection, laying a theoretical basis for rational design of the experimental process. |
| WOS关键词 | NONVIRAL VECTORS ; SIZE ; ENDOCYTOSIS ; COMPLEXES ; APOPTOSIS ; PATHWAYS ; POLYMERS ; TRAIL ; CELLS |
| 资助项目 | 973 Program, China[2014CB931900] ; NFSC, China[81673382] ; NFSC, China[81402883] ; NFSC, China[81422048] ; NFSC, China[81521005] ; Strategic Priority Research Program of CAS[XDA1205 0307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; CAS Scientific Research and Equipment Project[YZ2014 37] ; SANOFI-SIBS Scholarship Program ; Youth Innovation Promotion Association of CAS ; Fudan-SIMM Joint Research Fund[FU-SIMM201740 09] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000460134200005 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/290362]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Huang, Yongzhuo |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Guangzhou Univ Chinese Med, Inst Trop Med, Guangzhou 510405, Guangdong, Peoples R China 4.Univ Tradit Chinese Med, Affiliated Hosp Shandong, Jinan 250011, Shandong, Peoples R China 5.East China Normal Univ Sch Life Sci, Shanghai 200241, Peoples R China 6.Zhejiang Univ, Coll Chem & Biol Engn, Hangzhou 310027, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Wenyuan,Kang, Xuejia,Yuan, Bo,et al. Nano-Structural Effects on Gene Transfection: Large, Botryoid-Shaped Nanoparticles Enhance DNA Delivery via Macropinocytosis and Effective Dissociation[J]. THERANOSTICS,2019,9(6):1580-1598. |
| APA | Zhang, Wenyuan.,Kang, Xuejia.,Yuan, Bo.,Wang, Huiyuan.,Zhang, Tao.,...&Huang, Yongzhuo.(2019).Nano-Structural Effects on Gene Transfection: Large, Botryoid-Shaped Nanoparticles Enhance DNA Delivery via Macropinocytosis and Effective Dissociation.THERANOSTICS,9(6),1580-1598. |
| MLA | Zhang, Wenyuan,et al."Nano-Structural Effects on Gene Transfection: Large, Botryoid-Shaped Nanoparticles Enhance DNA Delivery via Macropinocytosis and Effective Dissociation".THERANOSTICS 9.6(2019):1580-1598. |
入库方式： OAI收割
来源：上海药物研究所
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