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Identification of a boron nitride nanosphere-binding peptide for the intracellular delivery of CpG oligodeoxynucleotides

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Title: Identification of a boron nitride nanosphere-binding peptide for the intracellular delivery of CpG oligodeoxynucleotides
Authors: Zhang, Huijie Browse this author
Yamazaki, Tomohiko Browse this author
Zhi, Chunyi Browse this author
Hanagata, Nobutaka Browse this author →KAKEN DB
Keywords: CpG oligodeoxynucleotides
drug delivery
boron nitride nanospheres
phage display
peptide
Issue Date: 21-Oct-2012
Publisher: Royal Society of Chemistry
Journal Title: Nanoscale
Volume: 4
Issue: 20
Start Page: 6343
End Page: 6350
Publisher DOI: 10.1039/c2nr31189e
PMID: 22941279
Abstract: CpG oligonucleotides (CpG ODNs) interact with Toll-like receptor 9 (TLR9), which results in the induction of immunostimulatory cytokines. We delivered CpG ODNs intracellularly using boron nitride nanospheres (BNNS). To enhance the loading capacity of CpG ODNs on BNNS, we used a phage display technique to identify a 12-amino acid peptide designated as BP7, with specific affinity for BNNS, and used it as a linker to load CpG ODNs on BNNS. The tyrosine residue (Y) at the eighth position from the N-terminus played a crucial role in the affinity of BP7 to BNNS. BNNS that bound BP7 (BNNS/BP7) were taken up into cells and showed no cytotoxicity, and CpG ODNs were successfully crosslinked with BP7 to create BP7-CpG ODNs conjugates. Using BP7 as a linker, the loading efficiency of CpG ODNs on BNNS increased 5-fold compared to the direct binding of CpG ODNs to BNNS. Furthermore, the BP7-CpG ODNs conjugates-loaded BNNS had a greater capacity to induce interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) than that of CpG ODNs directly loaded on BNNS. The higher amount of cytokine induction by BP7-CpG ODNs conjugates-loaded BNNS may be attributed to a higher loading capacity and stronger binding to BNNS with the linker BP7. The greater functionality of BP7-conjugated CpG ODNs on BNNS expands the potential of BNNS for drug delivery applications.
Rights: Nanoscale, 2012,4, 6343-6350 - Reproduced by permission of The Royal Society of Chemistry (RSC)
Type: article (author version)
URI: http://hdl.handle.net/2115/53012
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 花方 信孝

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