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Tumor specific delivery with redox-triggered mesoporous silica nanoparticles inducing neovascularization suppression and vascular normalization
Sun, Lu1,2; Liu, Yu-Jie1,2; Yang, Zhen-Zhen2; Qi, Xian-Rong1,2,3
刊名RSC ADVANCES
2015
DOI10.1039/c5ra09633b
5期:68页:55566-55578
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
资助者National Key Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education ; National Key Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education
研究领域[WOS]Chemistry
关键词[WOS]DRUG-DELIVERY ; GENE DELIVERY ; SOLID TUMORS ; CANCER ; SIRNA ; NANOCARRIERS ; DISEASES ; THERAPY ; GROWTH ; CELLS
英文摘要

RNA interference (RNAi) has great potential in cancer therapy, however, efficient cytoplasmic delivery still remains a major challenge. In this study, redox-responsive mesoporous silica nanoparticles with enlarged pores (denoted as MSN-siRNA/CrPEI) were designed by immobilizing polyethylenimine (PEI) via intermediate linkers of disulfide bonds onto the MSNs as caps for redox-responsive intracellular gene delivery. The MSN-siRNA/CrPEI with a high siRNA loading capacity (35 mg siRNA per g MSNs) could react to the specific reductive stimulation-upgraded glutathione concentration in tumor cells and release cargos through the rupture of disulfide bonds. Subsequently, MSN-siRNA/CrPEI was used to deliver VEGF siRNA for cancer therapy and the underlying mechanisms were explored. As we expected, MSN-siRNA/CrPEI could be readily internalized into cells, escaped from the endolysosomes and was distributed in the cytoplasm where siRNA mediated its function. MSN-siRNA/CrPEI showed remarkable anti-tumor efficacy by the suppression of neovascularization and vascular normalization after peritumoral application against mice with KB tumors, proved by interstitial fluid pressure (IFP) reduction, CD31 suppression and angioplerosis. Notably, siRNA combined with dexamethasone exerted a better treatment effect which is attributed to the strong capability of dexamethasone to decrease the IFP, and a lower IFP leads to an improvement in the delivery and efficacy of exogenously administered therapeutics. These results indicate that the tumor specific delivery of siRNA with redox-triggered mesoporous silica nanoparticles is a promising strategy to enhance therapeutic efficacy. Neovascularization suppression and vascular normalization may be beneficial for cancer inhibition.

语种英语
所属项目编号2013CB932501 ; 81273454 ; 81473156 ; 7132113 ; 20130001110055
资助者National Key Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education ; National Key Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education
WOS记录号WOS:000357051100096
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50855
专题北京大学药学院
作者单位1.Peking Univ, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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GB/T 7714
Sun, Lu,Liu, Yu-Jie,Yang, Zhen-Zhen,et al. Tumor specific delivery with redox-triggered mesoporous silica nanoparticles inducing neovascularization suppression and vascular normalization[J]. RSC ADVANCES,2015,5(68):55566-55578.
APA Sun, Lu,Liu, Yu-Jie,Yang, Zhen-Zhen,&Qi, Xian-Rong.(2015).Tumor specific delivery with redox-triggered mesoporous silica nanoparticles inducing neovascularization suppression and vascular normalization.RSC ADVANCES,5(68),55566-55578.
MLA Sun, Lu,et al."Tumor specific delivery with redox-triggered mesoporous silica nanoparticles inducing neovascularization suppression and vascular normalization".RSC ADVANCES 5.68(2015):55566-55578.
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