Sphk2 RNAi nanoparticles suppress tumor growth via downregulating cancer cell derived exosomal microRNA
文献类型：期刊论文
| 作者 | Liang, Jinying1,2,3; Zhang, Xinxin3 ; He, Shufang3; Miao, Yunqiu3; Wu, Na1; Li, Juan1; Gan, Yong3
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| 刊名 | JOURNAL OF CONTROLLED RELEASE
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| 出版日期 | 2018-09-28 |
| 卷号 | 286页码:348-357 |
| 关键词 | Exosomal miRNA Sphk2 siRNA silencing Nanoparticle HCC therapy |
| ISSN号 | 0168-3659 |
| DOI | 10.1016/j.jconrel.2018.07.039 |
| 文献子类 | Article |
| 英文摘要 | Exosomes secreted from cancer cells promote tumor progression through the transfection of containing microRNA (miRNA), mRNAs and proteins. Yet, little of this knowledge has translated into the therapeutic application. Herein, we propose a tumor therapeutic strategy via decreasing exosomal miRNA secretion. The study designed small interfering RNA (siRNA) loaded nanoparticles to downregulate sphingosine kinase 2 (Sphk2) and investigate their potential in decreasing exosomal oncogenic miRNA content and inhibiting tumor growth. The synthesized lipid (2E)-4-(dioleostearin)-amino-4-carbonyl-2-butenoic (DC) and chitosan were utilized to produce siRNA loaded nanoparticles (DC/CS-siRNA NPs), with optimal siRNA complexation and high transfection efficacy. We demonstrated that Sphk2 gene silencing induced by nanoparticles in hepatocellular carcinoma (HCC) cells could reduce miRNA-21 sorting into exosomes, contributing to the inhibition of tumor cell migration and tumorigenic function of exosomes to normal liver cells. Furthermore, in xenograft mouse model, Sphk2 siRNA loaded DC/CS NPs could significantly block tumor progression of malignancy HCC. These results suggest a new therapeutic approach for tumor treatment by ablating oncogenic miRNA in malicious exosomes. |
| WOS关键词 | HEPATOCELLULAR-CARCINOMA ; DRUG-DELIVERY ; MICROENVIRONMENT ; OSTEOPONTIN ; PROLIFERATION ; PROGRESSION ; METASTASIS |
| 资助项目 | National Natural Science Foundation of China[81571796] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2015229] ; SA-SIBS Scholarship Program[201411YF] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000444238000031 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279568]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Li, Juan; Gan, Yong |
| 作者单位 | 1.China Pharmaceut Univ, Dev Pharmaceut, Nanjing 210009, Jiangsu, Peoples R China; 2.Xinxiang Med Univ, Sch Pharm, Xinxiang 453003, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Liang, Jinying,Zhang, Xinxin,He, Shufang,et al. Sphk2 RNAi nanoparticles suppress tumor growth via downregulating cancer cell derived exosomal microRNA[J]. JOURNAL OF CONTROLLED RELEASE,2018,286:348-357. |
| APA | Liang, Jinying.,Zhang, Xinxin.,He, Shufang.,Miao, Yunqiu.,Wu, Na.,...&Gan, Yong.(2018).Sphk2 RNAi nanoparticles suppress tumor growth via downregulating cancer cell derived exosomal microRNA.JOURNAL OF CONTROLLED RELEASE,286,348-357. |
| MLA | Liang, Jinying,et al."Sphk2 RNAi nanoparticles suppress tumor growth via downregulating cancer cell derived exosomal microRNA".JOURNAL OF CONTROLLED RELEASE 286(2018):348-357. |
入库方式： OAI收割
来源：上海药物研究所
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