Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles
文献类型：期刊论文
| 作者 | Yu, Haijun3 ; Zou, Yonglong1,2; Jiang, Lei1,2; Yin, Qi3; He, Xinyu3; Chen, Lingli3; Zhang, Zhiwen3; Gu, Wangwen3; Li, Yaping3
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| 刊名 | BIOMATERIALS
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| 出版日期 | 2013-04 |
| 卷号 | 34期号:11页码:2738-2747 |
| 关键词 | Non-small cell lung cancer MDM2 pH-responsive Nanoparticles siRNA |
| ISSN号 | 0142-9612 |
| DOI | 10.1016/j.biomaterials.2012.12.042 |
| 文献子类 | Article |
| 英文摘要 | Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer caused human death. In this work, we selected oncogene mouse double minute 2 (MDM2) as a therapeutic target for NSCLC treatment and proposed that sufficient MDM2 knockdown could inhibit tumor growth via induction of cell cycle arrest and cancer cell apoptosis. On this regard, a new pH-responsive diblock copolymer of poly(methacryloyloxy ethyl phosphorylcholine)-block-poly(diisopropanolamine ethyl methacrylate) (PMPC-b-PDPA)/siRNA-MDM2 complex nanoparticle with minimized surface charge and suitable particle size was designed and developed for siRNA-MDM2 delivery in vitro and in vivo. The experimental results showed that the nanoparticles were spherical with particle size around 50 nm. MDM2 knockdown in p53 mutant NSCLC H2009 cells induced significant cell cycle arrest, apoptosis and growth inhibition through upregulation of p21 and activation of caspase-3. Furthermore, the growth of H2009 xenograft tumor in nude mice was inhibited via repeated injection of PMPC-b-PDPA/siRNA-MDM2 complex nanoparticles. These results suggested that PMPC-b-PDPA/siRNA complex nanoparticles targeting a unique set of oncogenes could be developed into a new therapeutic approach for NSCLC treatment. (c) 2013 Elsevier Ltd. All rights reserved. |
| WOS关键词 | SIRNA DELIVERY ; TARGETING MDM2 ; P53 ; EXPRESSION ; THERAPY ; PATHWAY ; AMPLIFICATION ; POLYMERS ; PROTEIN |
| 资助项目 | National Basic Research Program of China[2013CB932704] ; National Basic Research Program of China[2010CB934000] ; National Basic Research Program of China[2012CB932502] ; National Natural Science Foundation of China[30925041] ; National Natural Science Foundation of China[81270047] ; National Natural Science Foundation of China[81230029] |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000315748200017 |
| 出版者 | ELSEVIER SCI LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277682]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Li, Yaping |
| 作者单位 | 1.Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA 2.Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA; 3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yu, Haijun,Zou, Yonglong,Jiang, Lei,et al. Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles[J]. BIOMATERIALS,2013,34(11):2738-2747. |
| APA | Yu, Haijun.,Zou, Yonglong.,Jiang, Lei.,Yin, Qi.,He, Xinyu.,...&Li, Yaping.(2013).Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles.BIOMATERIALS,34(11),2738-2747. |
| MLA | Yu, Haijun,et al."Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles".BIOMATERIALS 34.11(2013):2738-2747. |
入库方式： OAI收割
来源：上海药物研究所
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