Delivery system of nucleic acid drug for protection of pollen allergy

• Project/Area Number: 22560777
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: National Institute for Materials Science
• Principal Investigator: HANAGATA Nobutaka 独立行政法人物質・材料研究機構, ナノテクノロジー融合ステーション, ステーション長 (10302796)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 生物機能工学 / CpGオリゴヌクレオチド / Toll-like receptor 9 / ドラッグデリバリー / ナノ粒子 / サイトカイン / シリコンナノ粒子 / メソ細孔シリカナノ粒子 / 窒化ホウ素ナノ粒子 / 花粉症

Research Abstract

We constructed delivery system of CpG oligodeoxynucleotide (CpG ODN) that is one of the useful drugs for treatment of allergic diseases such as pollen allergy. For the delivery, silicon nanoparticles (Si NPs) with 3.4 nm in average diameter were synthesized. Different immune-mediator cytokines were induced by CpG ODN bound to Si NPs with different binding modes. Simultaneous application of CpG ODN bound to Si NPs with both binding modes induced higher immune response.

Research Products

• [Journal Article] Recognition of CpG oligodeoxynucleotides by human Toll-like receptor 9 and subsequent cytokine induction (2013)
  • Author(s): S. Suwarti, T. Yamazaki, S. Chechetka, N. Hanagata
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 430 Issue: 4 Pages: 1234-1239
  • DOI: 10.1016/j.bbrc.2012.12.068
  • NAID: 120005228348
  • Peer Reviewed
• [Journal Article] Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system (2012)
  • Author(s): Hanagata, N
  • Journal Title: International Journal of Nanomedicine Volume: 7 Pages: 2181-2195
  • Peer Reviewed
• [Journal Article] Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucletotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α (2012)
  • Author(s): Manoharan Y., Ji Q., Yamazaki T., Shanmugavel C., Chen S., Ganesan S., Hill JP., Ariga K., Hanagata N.
  • Journal Title: International Journal of Nanomedicine Volume: 7 Pages: 3625-3635
  • Peer Reviewed
• [Journal Article] Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9 (2012)
  • Author(s): Chinnathambi S., Chen S., Ganesan S., Hanagata N
  • Journal Title: Scientific Reports Volume: 2 Pages: 534-534
  • NAID: 120004608970
  • Peer Reviewed
• [Journal Article] Identification of a boron nitride nanosphere-binding peptide for the intracellular delivery of CpG oligodeoxynucleotides (2012)
  • Author(s): Zhang H., Yamazaki T., Zhi C., Hanagata N
  • Journal Title: Nanoscale Volume: 4 Pages: 6343-6350
  • NAID: 120005306775
  • Peer Reviewed
• [Journal Article] T L R 9を介したC p G誘導サイトカインのナノ粒子によるスイッチング (2012)
  • Author(s): Hanagata N.
  • Journal Title: アレルギーの臨床 Volume: 32 Pages: 83-87
• [Journal Article] Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system (2012)
  • Author(s): N. Hanagata
  • Journal Title: Int. J. Nanomed. Volume: 7 Pages: 2181-2195
  • DOI: 10.2147/ijn.s30197
  • Peer Reviewed
• [Journal Article] Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α (2012)
  • Author(s): N. Hanagata, Manoharan, Q. Ji, Yamazaki, Shanmugavel, Chen, Ganesan, Hill and Ariga
  • Journal Title: Int. J. Nanomed. Volume: 7 Pages: 3625-3635
  • DOI: 10.2147/ijn.s32592
  • NAID: 120004448521
  • Peer Reviewed
• [Journal Article] Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9 (2012)
  • Author(s): Chinnathambi S., Chen S., Ganesan S., Hanagata N.
  • Journal Title: Scientific Reports Volume: 2(e-pub) Issue: 1 Pages: 534-534
  • DOI: 10.1038/srep00534
  • NAID: 120004608970
  • Peer Reviewed
• [Journal Article] TLR9を介したCpG誘導サイトカインのナノ粒子によるスイッチング (2012)
  • Author(s): 花方信孝
  • Journal Title: アレルギーの臨床 Volume: 32 Pages: 83-87
• [Journal Article] Design of mesoporous silica/CpG oligonucleaotides complexes for enhancement of delivery efficiency (2011)
  • Author(s): Zhu, Y., Meng, W., Li, X., Gao, H., Hanagata,N
  • Journal Title: The Journal of Physical Chemistry Volume: 115 Pages: 447-452
  • Peer Reviewed
• [Journal Article] BN nanospheres as CpG ODN carrier for activation of toll-like receptor 9 (2011)
  • Author(s): Zhi, C., Meng, W., Golberg, D., Tang, C., Hanagata, N.
  • Journal Title: Journal of Materials Chemistry Volume: 21 Pages: 5219-5222
  • Peer Reviewed
• [Journal Article] Dispersible shortened boron nitride nanotubes with improved molecular-loading capacity (2011)
  • Author(s): Zhi, C., Hanagata, N., Bando, Y., Golberg D.
  • Journal Title: Chemistry an Asian Journal Volume: 6 Pages: 2530-2535
  • Peer Reviewed
• [Journal Article] Hollow mesoporous silica/poly(L-lysine) particles for codelivery of drug and gene with enzyme-triggered release property (2011)
  • Author(s): Zhu, Y., Meng, W., Gao, H., Hanagata, N.
  • Journal Title: The Journal of Physical Chemistry C Volume: 115 Pages: 13630-13636
  • NAID: 120003504726
  • Peer Reviewed
• [Journal Article] Cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN)-capped hollow mesoporous silica particles for enzyme-triggered drug delivery (2011)
  • Author(s): Zhu, Y., Meng, W., Hanagata, N.
  • Journal Title: Dalton Transaction Volume: 40 Pages: 10203-10208
  • Peer Reviewed
• [Journal Article] Nuclease-resistant immunostimulatory phosphodiester CpG oligodeoxynucleotides as human Toll-like receptor 9 agonists (2011)
  • Author(s): Meng, W., Yamazaki, T., Nishida, Y., Hanagata, N
  • Journal Title: BMC Biotechnology Volume: 11 Pages: 88-88
  • NAID: 120003444328
  • Peer Reviewed
• [Journal Article] Hollow mesoporous silica/poly(L-lysine) particles for codelivery of drug and gene with enzyme-triggered release property (2011)
  • Author(s): Zhu, Y., Meng, W., Gao, H., Hanagata, N.
  • Journal Title: The Journal of Physical Chemistry Volume: 115 Issue: 28 Pages: 13630-13636
  • DOI: 10.1021/jp203454g
  • NAID: 120003504726
  • Peer Reviewed
• [Journal Article] Design of Mesoporous Silica/Cytosine-Phosphodiester-Guanine Oligodeoxynucleotide Complexes To Enhance Delivery Efficiency (2011)
  • Author(s): Zhu, Y., Meng, W., Li X., Gao H., Hanagata, N.
  • Journal Title: The Journal of Physical Chemistry Volume: 115 Issue: 2 Pages: 447-452
  • DOI: 10.1021/jp109535d
  • Peer Reviewed
• [Journal Article] Nuclease-resistant immunostimulatory phosphodiester CpG oligodeoxynucleotides as human Toll-like receptor 9 agonists (2011)
  • Author(s): Meng, W., Yamazaki, T., Nishida, Y., Hanagata, N.
  • Journal Title: BMC Biotechnology Volume: 11 Issue: 1 Pages: 88-96
  • DOI: 10.1186/1472-6750-11-88
  • NAID: 120003444328
  • Peer Reviewed
• [Journal Article] BN nanospheres as CpG ODN carrier for activation of toll-like receptor 9 (2011)
  • Author(s): Zhi, C., Meng, W., Yamazaki, T., Bando, Y., Golberg, D., Tang, C., Hanagata, N
  • Journal Title: Journal of Materials Chemistry Volume: (In press)
  • Peer Reviewed
• [Presentation] Regulation of bifurcated cytokine induction by binding mode of CpG DNA onto nanoparticles (2013)
  • Author(s): N. Hanagata
  • Organizer: 5th Immunotherapeutics & Immunomonitoring Conference
  • Place of Presentation: The Westin Gaslamp Quarter San Diego, USA
• [Presentation] N. New Nuclease-Resistant Immunostimulatory Phosphodiester-based Oligonucleotides for Immune Therapies (2012)
  • Author(s): Yamazaki, T.,Meng W., Hanagata
  • Organizer: The 9th World Biomaterials Congress (WBC)
  • Place of Presentation: Sichuan University,Sichuan China
• [Presentation] Preparation and characterization of silicon quantum dots for delivery of nucleic acid drugs. 4th International Conference on Advanced Nanomaterials (ANM2012) (2012)
  • Author(s): Shanmugavel, C., Ganesan S., Hanagata, N
  • Organizer: Indian Institute of Technology Madras (IIT Madras)
  • Place of Presentation: Chennai, India
• [Presentation] Regulation of Toll-like Receptor 9 mediated Cytokine Profile by Binding Mode of CpG Oligodeoxynucleotides to Nanoparticles (2012)
  • Author(s): Hanagata, N
  • Organizer: 1st International Conference on Emerging Advanced Nanomaterials (ICEAN 2012)
  • Place of Presentation: Mercure Hotel, Brisbane, Australia
• [Presentation] Synthesis and characterization of positively charged silicon quantum dots for delivery of nucleic acid drugs (2012)
  • Author(s): Shanmugavel, C., Hanagata, N
  • Organizer: 第6回 ナノバイオメディカル学会大会
  • Place of Presentation: 独立行政法人産業技術総合研究所
• [Presentation] Effect of interaction mode of CpG oligodeoxynucleotides with TLR9 on bifurcated cytokine induction (2012)
  • Author(s): Shanmugavel, C., Hanagata, N
  • Organizer: 第6回 ナノバイオメディカル学会大会
  • Place of Presentation: 独立行政法人産業技術総合研究所
• [Presentation] Identification of a specific binding peptide to boron nitride nanospheres for delivery of CpG oligodeoxynucleotides (2012)
  • Author(s): Zhang, H., Yamazaki, T., i Zhi, C., Hanagata, N.
  • Organizer: 第6回 ナノバイオメディカル学会大会
  • Place of Presentation: 独立行政法人産業技術総合研究所
• [Presentation] Response of human lung epithelial cells to the toxicity of zinc oxide nanoparticles (2012)
  • Author(s): Zhuang, F.,Hanagata, N.
  • Organizer: 第6回 ナノバイオメディカル学会大会
  • Place of Presentation: 独立行政法人産業技術総合研究所
• [Presentation] Characterization of interleukin-6 induction by natural CpG oligodeoxynuxleotide (2012)
  • Author(s): Chechetka, S., Yamazaki, T., Hanagata, N.
  • Organizer: 第6回 ナノバイオメディカル学会大会
  • Place of Presentation: 独立行政法人産業技術総合研究所
• [Presentation] Preparation and characterization of silicon quantum dots for delivery of nucleic acid drugs (2012)
  • Author(s): 7.Shanmugavel, C., Ganesan S., Hanagata
  • Organizer: 4th International Conference on Advanced Nanomaterials(ANM2012)
  • Place of Presentation: Indian Institute of Technology Madras
• [Presentation] Regulation of Toll-like Receptor 9 mediated Cytokine Profile by Binding Mode of CpG Oligodeoxynucleotides to Nanoparticles (2012)
  • Author(s): Hanagata, N.
  • Organizer: 1st International Conference on Emerging Advanced Nanomaterials
  • Place of Presentation: Mercure Hotel, Brisbane, Australia
• [Presentation] Analysis of CpG ODNS binding of human toll like receptor 9 (2011)
  • Author(s): Suwarti, Yamazaki, T., Hanagata, N.
  • Organizer: Infection and Immunity (Cold Spring Harbor Asia)
  • Place of Presentation: Dushu Lake Conference Center, Shuzou, China
  • Year and Date: 2011-09-08
• [Presentation] Novel CpG phosphodiester oligodeoxynucleotides as human toll-like receptor 9 agonists (2011)
  • Author(s): Yamazaki, T., Meng, W., Hanagata, N.
  • Organizer: Infection and Immunity (Cold Spring Harbor Asia)
  • Place of Presentation: Dushu Lake Conference Center, Shuzou, China
  • Year and Date: 2011-09-08
• [Presentation] Water soluble silicon quantum dots as fluorescent probes for bio-applications (2011)
  • Author(s): Chinnathambi S., Krishnan, V., Ariga, K., Hanagata, N.
  • Organizer: The Symposium on Micro/Nano Aspects of Biomaterials
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-07-19
• [Presentation] C-terminal ligand binding analysis of human Toll-like receptor 9 (2011)
  • Author(s): Suwarti, Yamazaki, T., Hanagata, N.
  • Organizer: The Symposium on Micro/Nano Aspects of Biomaterials
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-07-19
• [Presentation] Identification of Boron Nitride Nanospheres Binding Peptides (2011)
  • Author(s): Zhang, H., Yamazaki, T., Zhi, C., Hanagata, N.
  • Organizer: The Symposium on Micro/Nano Aspects of Biomaterials
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-07-19
• [Presentation] Novel Phosphodiester CpG Oligodeoxynucleotides with High Stimulatory Effects on Human Toll-like Receptor 9 (2011)
  • Author(s): Meng, W., Yamazaki, T., Hanagata, N.
  • Organizer: The Symposium on Micro/Nano Aspects of Biomaterials
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-07-19
• [Presentation] Design of mesoporous silica/CpG ODN complexes to enhance delivery efficiency. International Conference on Materials for Advanced (2011)
  • Author(s): Zhu, Y., Hanagata, N.
  • Organizer: International Conference on Materials for Advanced technologies
  • Place of Presentation: Suntec Singapore Hotel, Singapore
  • Year and Date: 2011-06-26
• [Presentation] CpG oligodeoxynucleotide and its delivery system (2011)
  • Author(s): Yamazaki, Y., Meng, W., Zhi, C., Zhu, Y., Hanagata, N.
  • Organizer: 9th annual Bio Nanotech Conference
  • Place of Presentation: Boston, US
  • Year and Date: 2011-06-16
• [Presentation] Construction of nuclear-resistant phosphodiester CpG oligonucleotides for pollinosis therapy (2011)
  • Author(s): Meng, W., Yamazaki, T., Hanagata, N.
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館(愛知県)
  • Year and Date: 2011-02-22
• [Presentation] BN nanospheres as CpG ODN carrier for activation of toll-like receptor 9 (2011)
  • Author(s): Zhi, C., Meng, W., Yamazaki, T., Bando, Y., Golberg, D., Tang, C., Hanagata, N.
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館(愛知県)
  • Year and Date: 2011-02-22
• [Presentation] Fe3O4@Sio2 hollow mesoporous spheres as potential carrier for anticancer drug delivery (2011)
  • Author(s): Zhu, Y., Hanagata, N
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館(愛知県)
  • Year and Date: 2011-02-22
• [Presentation] Design of mesoporous silica/CpG ODN complexes to enhance delivery efficiency (2011)
  • Author(s): Zhu, Y., Hanagata, N.
  • Organizer: International Conference on Materials for Advanced technologies
  • Place of Presentation: Suntec Singapore Hotel, Singapore
• [Presentation] Enhancement of the theraqeutic efficiency of a human toll-lilke receptor 9 agonist via bio-and nano-technology (2011)
  • Author(s): Yamazaki, T. Hanagata, N.
  • Organizer: International Workshop on Biomedical Sciences and Technologies
  • Place of Presentation: Anna University, Chennai, India
• [Presentation] Novel CpG oligodeoxynucleotide and its delivery system (2011)
  • Author(s): Yamazaki, Y., Meng, W., Zhi, C., Zhu, Y., Hanagata, N.
  • Organizer: 9th annual Bio Nanotech Conference
  • Place of Presentation: Boston, US
• [Presentation] Analysis of CpG ODNS binding of human toll like receptor 9 (2011)
  • Author(s): Suwarti, Yamazaki, T., Hanagata, N.
  • Organizer: Infection and Immunity (Cold Spring Harbor Asia)
  • Place of Presentation: Suzhou Dushu Lake Conference Center, Shuzou, China
• [Presentation] Novel CpG phosphodiester oligodeoxynucleotides as human toll-like receptor 9 agonists (2011)
  • Author(s): Yamazaki, T., Meng, W., Hanagata, N.
  • Organizer: Infection and Immunity (Cold Spring Harbor Asia)
  • Place of Presentation: Suzhou Dushu Lake Conference Center, Shuzou, China
• [Presentation] Construction of nuclear-resistant phosphodiester CpG oligonucleotides for pollinosis therapy (2011)
  • Author(s): Meng, W., Yamazaki, T., Hanagata, N.
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館
• [Presentation] Molecular organization at the live cell-biomembrane interface (2011)
  • Author(s): Zhang, L., Kaizuka, Y., Hanagata, N.
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館
• [Presentation] Fe3O4@Sio2 hollow mesoporous spheres as potential carrier for anticancer drug delivery (2011)
  • Author(s): Zhu, Y., Hanagata, N.
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館
• [Presentation] BN nanospheres as CpG ODN carrier for activation of toll-like receptor 9 (2011)
  • Author(s): Zhi, C., Meng, W., Yamazaki, T., Bando, Y., Golberg, D., Tang, C., Hanagata, N.
  • Organizer: ナノ・バイオメディカル学会
  • Place of Presentation: 名古屋大学野依記念学術交流会館
• [Presentation] Rattle-type Fe3O4@Sio2 hollow mesoporous spheres as potential carriers for anti-cancer drug delivery (2010)
  • Author(s): Zhu, Y., Hanagata, N
  • Organizer: The 10th Asia Bioceramics Symposium
  • Place of Presentation: Yogyakarta, Indonesia
  • Year and Date: 2010-11-03
• [Presentation] Hollow mesoporous silica spheres as carrier for drug delivery (2010)
  • Author(s): Zhu, Y., Hanagata, N
  • Organizer: 8th Annual Congress of International Drug Discovery Science
  • Place of Presentation: Beijing International Convention Center, Beijin, China
  • Year and Date: 2010-10-23
• [Presentation] Modified hollow mesopheres as carriers for targeted drug delivery (2010)
  • Author(s): Zhu, Y., Hanagata, N., Kobayashi, H
  • Organizer: 11th IUMRS International Conference in Asia
  • Place of Presentation: Qingdao International Convention Center, Qingdao, China
  • Year and Date: 2010-09-25
• [Patent(Industrial Property Rights)] 免疫刺激オリゴヌクレオチドおよび前記免疫刺激オリゴヌクレオチドを含む治療剤 (2011)
  • Inventor(s): 山崎智彦、花方信孝
  • Industrial Property Rights Holder: 独立行政法人物質・材料研究機構
  • Industrial Property Number: 2011-070049
  • Filing Date: 2011-03-28