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科研机构
中南大学 [1]
内容类型
期刊论文 [1]
发表日期
2013 [1]
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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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提交时间:2019/12/03
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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