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Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model 期刊论文
International Journal of Nanomedicine, 2013, 卷号: 8, 期号: 1, 页码: 3107-3118
作者:  Chen, Yan;  Yang, Lifang*;  Huang, Suping;  Li, Zhi;  Zhang, Lu
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DNAzymes are synthetic  single-stranded  catalytic nucleic acids that bind and cleave target mRNA in a sequence-specific manner  and have been explored for genotherapeutics. One bottleneck restricting their application is the lack of an efficient delivery system. As an inorganic nanomaterial with potentially wide application  nanohydroxyapatite particles (nHAP) have attracted increasing attention as new candidates for nonviral vectors. In this study  we developed an nHAP-based delivery system and explored its cellular uptake mechanisms  intracellular localization  and biological effects. Absorption of arginine-modified nanohydroxyapatite particles (Arg-nHAP) and DZ1 (latent membrane protein 1 [LMP1]-targeted) reached nearly 100% efficiency under in vitro conditions. Using specific inhibitors  cellular uptake of the Arg-nHAP/DZ1 complex was shown to be mediated by the energy-dependent endocytosis pathway. Further  effective intracellular delivery and nuclear localization of the complex was confirmed by confocal microscopy. Biologically  the complex successfully downregulated the expression of LMP1 in nasopharyngeal carcinoma cells. In a mouse tumor xenograft model  the complex was shown to be delivered efficiently to tumor tissue  downregulating expression of LMP1 and suppressing tumor growth. These results suggest that Arg-nHAP may be an efficient vector for nucleic acid-based drugs with potential clinical application.  


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