Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model

Authors Chen Y, Yang LF, Huang SP, Li Z, Zhang L, He J, Xu ZJ, Liu LY, Cao Y, Sun LQ

Received 15 May 2013

Accepted for publication 30 June 2013

Published 14 August 2013 Volume 2013:8(1) Pages 3107—3118

DOI https://doi.org/10.2147/IJN.S48321

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Video abstract presented by Lifang Yang

Views: 292

Yan Chen,1 Lifang Yang,1,2 Suping Huang,3 Zhi Li,1 Lu Zhang,1 Jiang He,1 Zhijie Xu,2 Liyu Liu,2 Ya Cao,2 Lunquan Sun1

1Center for Molecular Medicine, Xiangya Hospital, 2Cancer Research Institute, 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, People's Republic of China

Abstract: 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.

Keywords: hydroxyapatite nanoparticles, DNAzymes, latent membrane protein 1, transfection efficiency, cellular uptake

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

Rangger C, Helbok A, Sosabowski J, Kremser C, Koehler G, Prassl R, Andreae F, Virgolini IJ, von Guggenberg E, Decristoforo C

International Journal of Nanomedicine 2013, 8:4659-4671

Published Date: 5 December 2013

Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer

Lee HY, Mohammed KA, Kaye F, Sharma P, Moudgil BM, Clapp WL, Nasreen N

International Journal of Nanomedicine 2013, 8:4481-4494

Published Date: 21 November 2013

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Bian X, Liang S, John J, Hsiao CH, Wei X, Liang D, Xie H

International Journal of Nanomedicine 2013, 8:4521-4531

Published Date: 21 November 2013

Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats

Alarifi S, Ali D, Al-Doaiss AA, Ali BA, Ahmed M, Al-Khedhairy AA

International Journal of Nanomedicine 2013, 8:3937-3943

Published Date: 11 October 2013

Novel thermosensitive hydrogel for preventing formation of abdominal adhesions

Gao X, Deng XH, Wei XW, Shi HS, Wang FT, Ye TH, Shao B, Nie W,Li YL, Luo M, Gong CY, Huang N

International Journal of Nanomedicine 2013, 8:2453-2463

Published Date: 11 July 2013

Green synthesis of silver nanoparticles mediated by Pulicaria glutinosa extract

Khan M, Khan M, Adil SF, Tahir MN, Tremel W, Alkhathlan HZ, Al-Warthan A, Siddiqui MRH

International Journal of Nanomedicine 2013, 8:1507-1516

Published Date: 17 April 2013

Corrigendum

Hong SH, Kim JE, Kim YK, Minai-Tehrani A, Shin JY, Kang B, Kim HJ, Cho CS, Chae C, Jiang HL, Cho MH

International Journal of Nanomedicine 2012, 7:3069-3070

Published Date: 20 June 2012

Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

Yang FY, Teng MC, Lu M, Liang HF, Lee YR, Yen CC, Liang ML, Wong TT

International Journal of Nanomedicine 2012, 7:965-974

Published Date: 21 February 2012