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

Chitosan-coated boron nitride nanospheres enhance delivery of CpG oligodeoxynucleotides and induction of cytokines

Authors Zhang H, Chen S, Zhi C, Yamazaki T, Hanagata N

Received 25 January 2013

Accepted for publication 22 March 2013

Published 6 May 2013 Volume 2013:8(1) Pages 1783—1793

DOI https://doi.org/10.2147/IJN.S43251

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Huijie Zhang,1,2 Song Chen,3 Chunyi Zhi,4 Tomohiko Yamazaki,1,2 Nobutaka Hanagata1,2,5

1Graduate School of Life Science, Hokkaido University, Sapporo, Japan; 2Biomaterials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Ibaraki, Japan; 3Japanese Society for the Promotion of Science, Tokyo, Japan; 4Department of Physics and Materials Science, City University of Hong Kong, Hong Kong, People’s Republic of China; 5Nanotechnology Innovation Station, Ibaraki, Japan

Background: Cytosine-phosphate-guanine (CpG) oligodeoxynucleotides activate Toll-like receptor 9, leading to induction of proinflammatory cytokines, which play an important role in induction and maintenance of innate and adaptive immune responses. Previously, we have used boron nitride nanospheres (BNNS) as a carrier for delivery of unmodified CpG oligodeoxynucleotides to activate Toll-like receptor 9. However, because CpG oligodeoxynucleotides and BNNS are both negatively charged, electrostatic repulsion between them is likely to reduce the loading of CpG oligodeoxynucleotides onto BNNS. Therefore, the efficiency of uptake of CpG oligodeoxynucleotides is also limited and does not result in induction of a robust cytokine response. To ameliorate these problems, we developed a CpG oligodeoxynucleotide delivery system using chitosan-coated BNNS as a carrier.
Methods: To facilitate attachment of CpG oligodeoxynucleotides onto the BNNS and improve their loading capacity, we prepared positively charged BNNS by coating them with chitosan preparations of three different molecular weights and used them as carriers for delivery of CpG oligodeoxynucleotides.
Results: The zeta potentials of the BNNS-CS complexes were positive, and chitosan coating improved their dispersity and stability in aqueous solution compared with BNNS. The positive charge of the BNNS-CS complexes greatly improved the loading capacity and cellular uptake efficiency of CpG oligodeoxynucleotides. The loading capacity of the CpG oligodeoxynucleotides depended on the molecular weight of chitosan, which affected the positive charge density on the surface of the BNNS. CpG oligodeoxynucleotides loaded onto BNNS-CS complexes significantly enhanced production of interleukin-6 and tumor necrosis factor-a by peripheral blood mononuclear cells compared with CpG oligodeoxynucleotides directly loaded onto BNNS, or when Lipofectamine™ 2000 was used as the carrier. The molecular weight of the chitosan used to coat the BNNS affected the magnitude of cytokine induction by varying the strength of condensation of the CpG oligodeoxynucleotides.
Conclusion: Although the loading capacity of BNNS coated with low molecular weight chitosan preparations was the lowest of all the preparations, they induced the highest levels of cytokines.

Keywords: chitosan, boron nitride nanospheres, CpG oligodeoxynucleotides, drug delivery, cytokines

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:

Physicochemical properties of surface charge-modified ZnO nanoparticles with different particle sizes

Kim KM, Choi MH, Lee JK, Jeong J, Kim YR, Kim MK, Paek SM, Oh JM

International Journal of Nanomedicine 2014, 9:41-56

Published Date: 15 December 2014

Linear polyethylenimine produced by partial acid hydrolysis of poly(2-ethyl-2-oxazoline) for DNA and siRNA delivery in vitro

Fernandes JC, Qiu X, Winnik FM, Benderdour M, Zhang X, Dai K, Shi Q

International Journal of Nanomedicine 2013, 8:4091-4102

Published Date: 31 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

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Zhao TJ, Chen HZ, Dong YC, Zhang JJ, Huang HD, Zhu J, Zhang W

International Journal of Nanomedicine 2013, 8:1947-1957

Published Date: 16 May 2013

Application of the central composite design to optimize the preparation of novel micelles of harmine

Bei YY, Zhou XF, You BG, Yuan ZQ, Chen WL, Xia P, Liu Y, Jin Y, Hu XJ, Zhu QL, Zhang CG, Zhang XN, Zhang L

International Journal of Nanomedicine 2013, 8:1795-1808

Published Date: 6 May 2013

Bile salt/phospholipid mixed micelle precursor pellets prepared by fluid-bed coating

Dong F, Xie Y, Qi J, Hu F, Lu Y, Li S, Wu W

International Journal of Nanomedicine 2013, 8:1653-1663

Published Date: 26 April 2013

Multilayer bioactive glass/zirconium titanate thin films in bone tissue engineering and regenerative dentistry

Mozafari M, Salahinejad E, Shabafrooz V, Yazdimamaghani M, Vashaee D, Tayebi L

International Journal of Nanomedicine 2013, 8:1665-1672

Published Date: 26 April 2013

Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells

Chen CW, Lu DW, Yeh MK, Shiau CY, Chiang CH

International Journal of Nanomedicine 2011, 6:2567-2580

Published Date: 26 October 2011