Development of efficient gene transfection system by the combination use of dendritic cells-selective nanoparticle and physical stimulation for cancer therapy

• Project/Area Number: 19689005
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: KAWAKAMI Shigeru Kyoto University, 薬学研究科, 講師 (20322307)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2010: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2007: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
• Keywords: 医療・福祉 / 免疫学 / 癌 / 遺伝子 / ドラッグデリバリー / 遺伝子治療 / 遺伝子デリバリー / DNAワクチン / ターゲティング / ドラッグデリバリーシステム / メラノーマ / ソノポレーション / 非ウイルスキャリア / マンノース修飾リポソーム / リポソーム / DDS

Research Abstract

In this study, we developed mannosylated bubble lipoplex for ultrasound-responsive and cell-selective gene transfer. After administration of mannosylated bubble lipoplex, plasmid DNA was efficiently transfected to the mannose receptors-expressing cells, including dendritic cells and liver non-parenchymal cells followed by ultrasound exposure. Enhanced DNA vaccine potency was also observed by this transfection method.

Research Products

• [Journal Article] The elucidation of gene transferring mechanism by ultrasound-responsive unmodified and mannose-modified lipoplexes (2011)
  • Author(s): Un K, Kawakami S, Yoshida M, Higuchi Y, Suzuki R, Maruyama K, Yamashita F, Hashida M
  • Journal Title: Biomaterials 32(20) Pages: 4659-4669
  • Peer Reviewed
• [Journal Article] Suppression of melanoma growth and metastasis by DNA vaccination using an ultrasound-responsive and mannose-modified gene carrier (2011)
  • Author(s): Un K, Kawakami S, Suzuki R, Maruyama K, Yamashita F, Hashida M
  • Journal Title: Mol Pharm 8(2) Pages: 543-554
  • Peer Reviewed
• [Journal Article] Suppression of melanoma growth and metastasis by DNA vaccination using an ultrasound-responsive and mannose-modified gene carrier (2011)
  • Author(s): K.Un, S.Kawakami, R.Suzuki, K.Maruyama, F.Yamashita, M.Hashida
  • Journal Title: Molecular Pharmaceutics Volume: 8(2) Pages: 543-554
  • Peer Reviewed
• [Journal Article] Development of an ultrasound-responsive and mannose-modified gene carrier for DNA vaccine therapy (2010)
  • Author(s): Un K, Kawakami S, Suzuki R, Maruyama K, Yamashita F, Hashida M
  • Journal Title: Biomaterials 31(30) Pages: 7813-7826
  • Peer Reviewed
• [Journal Article] Enhanced transfection efficiency into macrophages and dendritic cells by a combination method using mannosylated lipoplexes and bubble liposomes with ultrasound exposure (2010)
  • Author(s): Un K, Kawakami S, Suzuki R, Maruyama K, Yamashita F, Hashida M
  • Journal Title: Hum Gene Ther 21(1) Pages: 65-74
  • Peer Reviewed
• [Journal Article] Intranasal administration of CpG DNA lipoplex prevents pulmonary metastasis in mice (2010)
  • Author(s): Zhou S, Kawakami S, Yamashita F, Hashida M
  • Journal Title: Cancer Lett 287(1) Pages: 75-81
  • Peer Reviewed
• [Journal Article] Development of an ultrasound-responsive and mannose-modified gene carrier for DNA vaccine therapy (2010)
  • Author(s): K.Un, S.Kawakami, R.Suzuki, K.Maruyama, F.Yamashita, M.Hashida
  • Journal Title: Biomaterials Volume: 31(30) Pages: 7813-7826
  • Peer Reviewed
• [Journal Article] Intranasal administration of CpG DNA lipoplex prevents pulmonary metastasis in mice (2010)
  • Author(s): Zhou S, Kawakami S, Yamashita F, Hashida M
  • Journal Title: Cancer Lett. 287(1) Pages: 75-81
  • Peer Reviewed
• [Journal Article] Enhanced transfection efficiency into macrophages and dendritic cells by a combination method using mannosylated lipoplexes and bubble liposomes with ultrasound exposure (2010)
  • Author(s): K.Un, S.Kawakami, R.Suzuki, K.Maruyama, F.Yamashita, M.Hashida
  • Journal Title: Human Gene Therapy Volume: 21(1) Pages: 65-74
  • Peer Reviewed
• [Journal Article] Intranasal administration of CpG DNA lipoplex prevents pulmonary metastasis in mice (2010)
  • Author(s): S.Zhou, S.Kawakami, F.Yamashita, M.Hashida
  • Journal Title: Cancer Letters Volume: 287(1) Pages: 75-81
  • Peer Reviewed
• [Journal Article] Mannosylated cationic liposomes/CpG DNA complex for the treatment of hepatic metastasis after intravenous administration in mice (2009)
  • Author(s): Kuramoto Y, Kawakami S, Zhou S, Fukuda K, Yamashita F, Hashida M
  • Journal Title: J Pharm Sci 98(3) Pages: 1193-1197
  • Peer Reviewed
• [Journal Article] Mannosylated cationic liposomes/CpG DNA complex for the treatment of Hepatic metastasis after intravenous administration in mice (2009)
  • Author(s): Yukari Kuramoto, et.al.
  • Journal Title: Journal of Pharmaceutical Sciences 98(3) Pages: 1193-1197
  • Peer Reviewed
• [Journal Article] Non-viral approaches for targeted delivery of plasmid DNA and oligonucleotide (2008)
  • Author(s): Kawakami S, Higuchi Y, Hashida M
  • Journal Title: J Pharm Sci 97(2) Pages: 726-745
  • Peer Reviewed
• [Journal Article] Use of mannosylated cationic liposomes/ immunostimulatory CpG DNA complex for effective inhibition of peritoneal dissemination in mice (2008)
  • Author(s): Kuramoto Y, Kawakami S, Zhou S, Fukuda K, Yamashita F, Hashida M
  • Journal Title: J Gene Med 10(4) Pages: 392-399
  • Peer Reviewed
• [Journal Article] Efficient peritoneal dissemination treatment obtained by an immunostimulatory phosphorothioate-type CpG DNA/cationic liposome complex in mice (2008)
  • Author(s): Kuramoto Y, Kawakami S, Zhou S, Fukuda K, Yamashita F, Hashida M
  • Journal Title: J Control Release 126(3) Pages: 274-280
  • Peer Reviewed
• [Journal Article] Efficient targeting to alveolar macrophages by intratracheal administration of mannosylated liposomes in rats (2008)
  • Author(s): Wijagkanalan W, Kawakami S, Takenaga M, Igarashi R, Yamashita F, Hashida M
  • Journal Title: J Control Release 125(2) Pages: 121-130
  • Peer Reviewed
• [Journal Article] Efficient peritoneal dissemination treatment obtained by an immunostimulatory phosphorothioate-type CpG DNA/cationic liposome complex in mic (2008)
  • Author(s): Kuramoto Y, Kawakami S, Zhou S, Fukuda K, Yamashita F, Hashida M
  • Journal Title: J Control Release 126(3) Pages: 274-280
  • Peer Reviewed
• [Journal Article] Efficient targeting to alveolar macrophages by intratracheal administration of mannosylated liposomes in rats (2008)
  • Author(s): Wassana Wijagkanalan, et.al.
  • Journal Title: Journal of Controlled Release 125 (2) Pages: 121-130
  • Peer Reviewed
• [Journal Article] Use of mannosylated cationic liposomes/immunostimulatory CpG DNA complex for effective inhibition of peritoneal dissemination in mice (2008)
  • Author(s): Yukari Kuramoto, et.al.
  • Journal Title: Journal of Gene Medicine 10 Pages: 392-399
  • Peer Reviewed
• [Journal Article] Efficient peritoneal dissemination treatment obtained by an immunostimulatory phosphorothioate-type CpG (2008)
  • Author(s): Y. Kuramoto, S. Kawakami, S. Zhou, K. Fukuda, F. Yamashita, M.
  • Journal Title: Journal of Controlled Release 126 Pages: 274-280
  • Peer Reviewed
• [Journal Article] Development of an antigen presenting cell-targeted DNA vaccine against melanoma by mannosyated liposomes (2007)
  • Author(s): Lu Y, Kawakami S, Yamashita F, Hashida M
  • Journal Title: Biomaterials 28(21) Pages: 255-3262
  • Peer Reviewed
• [Journal Article] Development of an antigen presenting cell-targeted DNA vaccine against melanoma by mannosylated liposomes (2007)
  • Author(s): Y. Lu, S. Kawakami, F. Yamashita, M. Hashida
  • Journal Title: Biomaterials 28 Pages: 3255-3262
  • Peer Reviewed
• [Journal Article] Optimization of tumor-selective targeting by basic fibroblast growth factor-binding peptide grafted (2007)
  • Author(s): T. Terada, M. Mizobata, S. Kawakami, F. Yamashita, M.
  • Journal Title: Journal of Controlled Release 119 Pages: 262-270
  • Peer Reviewed
• [Presentation] Gene transfer characteristics of an ultrasound-responsive and mannose-modified bubble lipoplex (2011)
  • Author(s): Kawakami S, Un K, Suzuki R, Maruyama K, Higuchi Y, Yamashita F, Hashida M
  • Organizer: International Conference on Biomaterials Sciences
  • Place of Presentation: Tsukuba
  • Year and Date: 2011-03-17
• [Presentation] Gene transfection characteristics of an ultrasound-responsive and mannose-modified bubble lipoplex (2011)
  • Author(s): S.Kawakami, K.Un, R.Suzuki, K.Maruyama, Y.Higuchi, F.Yamashita, M.Hashida
  • Organizer: International Conference on Biomaterials Science 2011
  • Place of Presentation: International Congress Center (Tsukuba, Japan)
  • Year and Date: 2011-03-17
• [Presentation] 超音波応答性リポソームを用いたin-vivo遺伝子導入法における転写因子活性化と炎症性サイトカイン産生の評価 (2010)
  • Author(s): 運敬太、川上茂、鈴木亮、丸山一雄、樋口ゆり子、山下富義、橋田充
  • Organizer: 遺伝子・デリバリー研究会第10回シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-02
• [Presentation] 超音波応答性リポソームを用いたin-vivo遺伝子導入法における転写因子活性化と炎症性サイトカイン産生の評価 (2010)
  • Author(s): 運敬太、川上茂、鈴木亮、丸山一雄、樋口ゆり子、山下富義、橋田充
  • Organizer: 遺伝子・デリバリー研究会第10回シンポジウム
  • Place of Presentation: 北海道大学 学術交流会館(札幌)
  • Year and Date: 2010-06-02
• [Presentation] マンノース修飾バブルリポプレックスと超音波照射による標的細胞選択的かつ高効率遺伝子導入法の開発 (2010)
  • Author(s): 運敬太、川上茂、鈴木亮、丸山一雄、山下富義、橋田充
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] マンノース修飾バブルリポプレックスと超音波照射による標的細胞選択的かつ高効率遺伝子導入法の開発 (2010)
  • Author(s): 運敬太、川上茂、鈴木亮、丸山一雄、山下富義、橋田充
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: ホテルグランヴィア岡山(岡山)
  • Year and Date: 2010-03-29
• [Presentation] Development and evaluation of organ-press mediated in vivo gene transfection methods of plasmid DNA and siRNA. (2009)
  • Author(s): Kawakami S, Mukai H, Hashida M
  • Organizer: The 10 the US-Japan Symposium on Drug Delivery Systems
  • Place of Presentation: Maui, Hawaii
  • Year and Date: 2009-12-17
• [Presentation] Cancer immuno -therapy using glycosylated liposomes (2009)
  • Author(s): Kawakami S, Hashida M
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] Cancer immunotherapy using glycosylated liposomes (2009)
  • Author(s): Kawakami S, Hashida M
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] Cancer immunotherapy using glycosylated liposomes (2009)
  • Author(s): S.Kawakami, M.Hashida
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-10-02
• [Presentation] 新規マンノース修飾バブルリポプレックスと超音波の併用による標的細胞選択的in vivo遺伝子導入法の開発 (2009)
  • Author(s): 運敬太、川上茂、丸山一雄、山下富義、橋田充
  • Organizer: 日本薬剤学会第24年会
  • Place of Presentation: 静岡県コンベンションセンター(静岡)
  • Year and Date: 2009-05-21
• [Presentation] Glycosylated liposomes for drug and nucleic acids delivery (2008)
  • Author(s): Kawakami S, Higuchi Y, Hashida M
  • Organizer: 11th Liposome Research Days
  • Place of Presentation: Yokohama
  • Year and Date: 2008-07-21
• [Presentation] Glycosylated liposomes for drug and nucleic acids delivery (2008)
  • Author(s): Kawakami S, Higuchi Y, Hashida M
  • Organizer: 11th Liposome Research Days
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2008-07-21
• [Presentation] Glycosylated liposomes for the targeted delivery of siRNA and CpG DNA (2008)
  • Author(s): Kawakami S, Higuchi Y, Yamashita F, Hashida M
  • Organizer: 第14回日本遺伝子治療学会年会
  • Place of Presentation: 札幌
  • Year and Date: 2008-06-12
• [Presentation] Glycosylated liposomes for the targeted delivery of siRNA and CpG DNA (2008)
  • Author(s): Shigeru Kawakami, Yuriko Higuchi, Fumivoshi Yamashita, Mitsuru Hashida
  • Organizer: 第14回日本遺伝子治療学会
  • Place of Presentation: 札幌医科大学
  • Year and Date: 2008-06-12
• [Presentation] Targeting of inhaled dexamethasone palmitate using mannosylated liposomes in an endotoxin-induced lung inflammation model (2008)
  • Author(s): Wijagkanalan W, Kawakami S, Teshima M, Sasaki H, Hashida M
  • Organizer: 日本薬剤学会第23年会
  • Place of Presentation: 札幌
  • Year and Date: 2008-05-20
• [Presentation] argeting of inhaled dexamethasone palmitate using mannosy lated liposomes in an endotoxin-induced lung inflammation model (2008)
  • Author(s): Wassana Wijagkanalan, Shigeru Kawakami, Mugen leshima, Hitoshi Sasaki, Mitsuru Hashida
  • Organizer: 日本薬剤学会第23年会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2008-05-20
• [Presentation] 圧力による腎臓への核酸導入法 (2008)
  • Author(s): 向井英更、川上茂、馬凡、高橋晴之、山下富義、橋阻充
  • Organizer: 遺伝子・デリバリー研究会第8回シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2008-05-09
• [Presentation] Evaluation and development of nano-carriers using imaging technology (2007)
  • Author(s): Kawakami S, Hashida M
  • Organizer: 1st Asian Biomaterial Conference
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2007-12-08
• [Presentation] Cationic liposomes formulations for the effective treatment of peritoneal dissemination by CpG DNA (2007)
  • Author(s): Kuramoto Y, Kawakami S, Hashida M
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Cationic liposomes formulations for the effective treatment of peritoneal dissemination by CpG DNA (2007)
  • Author(s): Kuramoto Y, Kawakami S, Hashida M
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Book] バイオ医薬の開発技術とシーズ、第5編非感染症ワクチン(がんワクチン他)、第3章がんDNAワクチンの為のリポソーム製剤の開発 (2008)
  • Author(s): 川上茂、樋口ゆり子、橋田充
  • Publisher: CMC出版社
• [Book] バイオ医薬の開発技術とシーズ(第5編非感染症ワクチン(がんワクチン他)、第3章がんDNAワクチンの為のリポソーム製剤の開発) (2008)
  • Author(s): 川上茂、樋口ゆり子、橋田充
  • Publisher: CMC出版社
• [Remarks] ホームページ
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• [Remarks]
  • URL: http://dds.pharm.kyoto-u.ac.jp/Dds_Home/index.htm