Nucleic acid-based nanomachine systems for tumor treatment

• Project/Area Number: 20240049
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Kyushu University
• Principal Investigator: MARUYAMA Atsushi Kyushu University, 先導物質化学研究所, 教授 (40190566)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥48,880,000 (Direct Cost: ¥37,600,000、Indirect Cost: ¥11,280,000); Fiscal Year 2010: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000); Fiscal Year 2009: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2008: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
• Keywords: 機能性核酸 / 核酸シャペロン / 医薬送達システム / 高分子電解質複合体 / グラフトコポリマー / 構造転移 / ナノマシン / ポリカチオン / くし型共重合体 / DNA / 高次構造転移 / 核酸4重鎖

Research Abstract

In this research project, we studied polymer materials to construct therapeutic nanomachine systems for tumor treatment. Polymer materials that accumulates in tumor tissues and exhibits nucleic acid chaperoning activity were designed and evaluated. Cationic comb-type copolymers having hydrophilic graft chains were found to accumulate effectively in tumor tissue subcutaneously implanted in mice. The copolymer was also found to facilitate structural transition between stem-loop structure and duplex and assembly of quadruplex DNA. These results suggested that activity of functional nucleic acids could be regulated with the cationic copolymers at tumor sites.

Research Products

• [Journal Article] A mirror-image tetramolecular DNA quadruplex (2011)
  • Author(s): P.L.T.Tran, R.Moriyama, A.Maruyama, B.Rayner, J.L.Mergny
  • Journal Title: Chem.Commun. 47in press Pages: 5437-5439
  • Peer Reviewed
• [Journal Article] Cationic comb-type copolymers do not cause collapse but shrinkage of DNA molecules (2011)
  • Author(s): N.Sonda, M.Hirano, N.Shimada, A.Kano, S.Kidoaki, A.Maruyama
  • Journal Title: Chem Lett 40 Pages: 250-251
  • NAID: 10027815446
  • Peer Reviewed
• [Journal Article] DNA assembly and reassembly activated by cationic comb-type copolymer (2011)
  • Author(s): R.Moriyama, N.Shimada, A.Kano, A.Maruyama
  • Journal Title: Biomaterials 32 Pages: 2351-2358
  • Peer Reviewed
• [Journal Article] Grafting of poly (ethylene glycol) to poly-lysine augments its lifetime in blood circulation and accumulation in tumors without loss of the ability to associate with siRNA (2011)
  • Author(s): A.Kano, K.Moriyama, T.Yamano, I.Nakamura, N.Shimada, A.Maruyama
  • Journal Title: J.Controlled Rel. 149 Pages: 2-7
  • NAID: 120004951559
  • Peer Reviewed
• [Journal Article] Grafting of poly(ethylene glycol) to poly-lysine augments its lifetime in blood circulation and accumulation in tumors without loss of the ability to associate with siRNA (2011)
  • Author(s): A.Kano, K.Moriyama, T.Yamano, I.Nakamura, N.Shimada, A.Maruyama
  • Journal Title: J.Controlled Rel. Volume: (in press)
  • NAID: 120004951559
  • Peer Reviewed
• [Journal Article] Controlled synthesis of PEI-coated gold nanoparticles using reductive catechol chemistry for siRNA delivery (2011)
  • Author(s): Y.Lee, S.H.Lee, J.S.Kim, A.Maruayma, X.Chen, T.G.Park
  • Journal Title: J.Controlled Rel. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates (2011)
  • Author(s): T.Ishihara, A.Kano, K.Obara, M.Saito, X.Chen, T.G.Park, T.Akaike, A.Maruyama
  • Journal Title: J.Controlled Rel. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Evaluation of polyanion-coated biodegradable polymeric micelles as drug delivery vehicles (2011)
  • Author(s): H.Tian, L.Lin, J.Chen, X.Chen, T.G.Park, A.Maruyama
  • Journal Title: J.Controlled Rel. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cationic comb-type copolymers do not cause collapse but shrinkage of DNA molecules (2011)
  • Author(s): H.Tian, L.Lin, J.Chen, X.Chen, T.G.Park, A.Maruyama
  • Journal Title: J.Controlled Rel. Volume: (in press)
  • NAID: 10027815446
  • Peer Reviewed
• [Journal Article] RGD targeting hyaluronic acid coating system for PEI-PBLG polycation gene carriers (2011)
  • Author(s): H.Tian, L.Lin, J.Chen, X.Chen, T.G.Park, A.Maruyama
  • Journal Title: J.Controlled Rel. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cationic graft copolymer as a DNA B-Z transition inducer : Effect of copolymer structure (2010)
  • Author(s): N.Shimada, M.Yamamoto, A.Kano, A.Maruayma
  • Journal Title: Biomacromolecules 11 Pages: 3043-3048
  • Peer Reviewed
• [Journal Article] Preparation of Biodegradable Polymer Micelle Exhibiting High Stability by Coating with Polyion Complex (2010)
  • Author(s): Y.Ohya, S.Takeda, Y.Shibata, T.Ouchi, A.Maruyama
  • Journal Title: Macromol. Biosci. 211 Pages: 1750-1756
  • Peer Reviewed
• [Journal Article] Unusually large hysteresis of temperature-responsive poly(N-ethyl-2-propionamidoacrylamide) studied by microcalorimetry and FT-IR (2010)
  • Author(s): M.R.Berber, H.Mori, I.H.Hafez, K.Minagawa, M.Tanaka, T.Niidome, Y.Katayama, A.Maruyama T.Hirano, Y.Maeda, T.Mori
  • Journal Title: J Phys Chem B. Volume: 114 Pages: 7784-90
  • Peer Reviewed
• [Journal Article] Synthesis, characterization and drug release of biocompatible/biodegradable non-toxic poly(urethaneurea)s based on poly(ε-caprolactone)s and lysine-based diisocyanate (2010)
  • Author(s): T.T.Reddy, A.Kano, A.Maruyama, A.Takahara
  • Journal Title: J.Biomater.Sci. Volume: 21 Pages: 1483-1502
  • Peer Reviewed
• [Journal Article] Preparation of Biodegradable Polymer Micelle Exhibiting High Stability by Coating with Polyion Complex (2010)
  • Author(s): Y.Ohya, S.Takeda, Y.Shibata, T.Ouchi, A.Maruyama
  • Journal Title: Macromol.Biosci. Volume: 211 Pages: 1750-1756
  • Peer Reviewed
• [Journal Article] Cationic graft copolymer as a DNA B-Z transition inducer : Effect of copolymer structure (2010)
  • Author(s): N.Shimada, M.Yamamoto, A.Kano, A.Maruayma
  • Journal Title: Biomacromolecules Volume: 11 Pages: 3043-3048
  • Peer Reviewed
• [Journal Article] B-Z DNA transition triggered by a cationic comb-type copolymer (2009)
  • Author(s): N.Shimada, A.Kano, A.Maruyama
  • Journal Title: Adv.Funct.Mater. 19 Pages: 3590-3595
  • Peer Reviewed
• [Journal Article] Interaction of self-assembled cationic nanogels with oligo-DNA and function as artificial nucleic acid chaperone (2009)
  • Author(s): N.Morimoto, J.Tamada, S.Sawada, N.Shimada, A.Kano, A.Maruyama, K.Akiyoshi
  • Journal Title: Chem.Lett. 38 Pages: 496-497
  • NAID: 10025122311
  • Peer Reviewed
• [Journal Article] Synergistic stabilization of nucleic acid assembly by 2'-O,4'-C-methylene bridged nucleic acid modification and additions of comb-type cationic copolymers (2009)
  • Author(s): H.Torigoe, A.Maruyama, S.Obika, T.Imanishi, T. Katayama
  • Journal Title: Biochemistry 48 Pages: 3545-3553
  • Peer Reviewed
• [Journal Article] Liver endothelial cell uptake of enzymatically digested hyaluronan in vivo and in vitro (2009)
  • Author(s): S.Mochizuki, A.Kano, N.Shimada, A.Maruyama
  • Journal Title: J.Biomater. Sci.Polym.Ed. 20 Pages: 83-97
  • Peer Reviewed
• [Journal Article] B-Z DNA Transition Triggered by a Cationic Comb-Type Copolymer (2009)
  • Author(s): Naohiko Shimada, Arihiro Kano, Atsushi Maruyama
  • Journal Title: Advanced Functional Materials 19 Pages: 3590-3595
  • Peer Reviewed
• [Journal Article] Interaction of Self-assembled Cationic Nanogels with Oligo-DNA and Function as Artificial Nucleic Acid Chaperone (2009)
  • Author(s): Morimoto, N., Tamada, J., Sawada, S., Shimada, N., Kano, A., Maruyama, A., Akiyoshi, K.
  • Journal Title: Chemistry Letters 38 Pages: 496-497
  • NAID: 10025122311
  • Peer Reviewed
• [Journal Article] A highly efficient siRNA carrier of PBLG modified hyperbranched PEI (2009)
  • Author(s): Chen, J., Tian, H., Guo, Z., Xia, J., Kano, A., Maruyama, A., Jing, X., Chen, X.
  • Journal Title: Macromol Biosci 9 Pages: 1247-1253
  • Peer Reviewed
• [Journal Article] Liver endothelial cell uptake of enzymatically digested hyaluronan in vivo and in vitro (2009)
  • Author(s): Mochizuki, et al
  • Journal Title: J. Biomater. Sci., Polym. Ed. 20 Pages: 83-97
  • Peer Reviewed
• [Journal Article] A Biomimetic Alternative to PEG as an Antifouling Coating : Resistance to Non-Specific Protein Adsorption of Poly(L-lysine)-graft-Dextran (2008)
  • Author(s): C.Perrino, S.Lee, S.W.Choi, A.Maruyama, N.D.Spencer
  • Journal Title: Langmuir 24 Pages: 8850-8856
  • Peer Reviewed
• [Journal Article] Kinetic effect of cationic comb-type copolymers on DNA hybridization (2008)
  • Author(s): A.Maruyama, L.Wu, N.Shimada, A.Kano
  • Journal Title: Adv.Mater.Res.
  • Peer Reviewed
• [Journal Article] Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life (2008)
  • Author(s): A.Kano, T.Yamano, S.W.Choi, A.Maruyama
  • Journal Title: Adv.Mater.Res.
  • Peer Reviewed
• [Journal Article] Polymer brush-stabilized polyplex for a siRNA carrier with long blood circulatory half-life (2008)
  • Author(s): Kano, et al
  • Journal Title: Adv. Mater. Res. 47-50 Pages: 762-764
  • Peer Reviewed
• [Journal Article] Kinetic effect of cationic comb-type copolymers on DNA hybridization, 47-50, 1355-1358 (2008). (2008)
  • Author(s): Maruyama, et al
  • Journal Title: Adv. Mater. Res. 47-50 Pages: 1355-1358
  • Peer Reviewed
• [Journal Article] A. Maruyama, Evaluation of polyanion-coated biodegradable polymeric micelles as drug delivery vehicles
  • Author(s): Y.Ohya, S.Takeda, Y.Shibata, T.Ouchi, A.Kano, T.Iwata, S.Mochizuki, Y.Taniwaki
  • Journal Title: J.Controlled Rel. in press
  • Peer Reviewed
• [Journal Article] Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates
  • Author(s): T.Ishihara, A.Kano, K.Obara, M.Saito, X.Chen, T.G.Park, T.Akaike, A.Maruyama
  • Journal Title: J.Controlled Rel. in press
  • Peer Reviewed
• [Presentation] Manipulation of DNA quadruplex assembly with cationic copolymers」と「Poly(allylamine) derivatives exhibiting UCST-type solution bihavior under physiological conditions (2010)
  • Author(s): 丸山厚
  • Organizer: PACIFI CHEM 2010
  • Place of Presentation: Hawaii Convention Center ; Hilton Hawaiian Village ; Sheraton Waikiki ; the Royal Hawaiian Hotel
  • Year and Date: 2010-12-17
• [Presentation] αアミノ酸のpH感受性に着目した遺伝子キャリア設計 (2010)
  • Author(s): 丸山厚, ほか
  • Organizer: 第32回日本バイオマテリアル学会大会
  • Place of Presentation: グランドプリンスホテル(広島)
  • Year and Date: 2010-11-29
• [Presentation] Catiotic comb-type Copolymer to Manipulate DNA hybridization and Folding and Its Application to DNA Nanobiotechnology (2010)
  • Author(s): 丸山厚
  • Organizer: 2010 ISOMRM
  • Place of Presentation: International Cnvention Center/N H R Institute TAIWAN
  • Year and Date: 2010-11-04
• [Presentation] ポリ(L-リシン)-グラフト-ポリエチレングリコール共重合体(PLL-g-PEG)の光線力学療法剤ポルフィマーナトリウムとの相互作用と腫瘍デリバリー (2010)
  • Author(s): 丸山厚
  • Organizer: 第59回高分子学会討論会
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2010-09-15
• [Presentation] Recognition of sulfated hyaluronic acid by liver sinusoidal endothelial cells (2010)
  • Author(s): 丸山厚, ほか
  • Organizer: 第8回ヒアルロン酸国際カンファレンス
  • Place of Presentation: 京都ブライトンホテル(京都)
  • Year and Date: 2010-06-08
• [Presentation] Dimerization of stem-loop DNA by cationic comb-type copolymers (2010)
  • Author(s): 丸山厚
  • Organizer: 弟59回高分子学会年次大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2010-05-27
• [Presentation] Invited speaker, 2010 International Symposium of Materials on Regenerative Medicine (2010 ISOMRM) (2010)
  • Author(s): A.Maruyama
  • Organizer: Cationic comb-type copolymer to manipulate DNA hybridization and folding and its application to DNA nanobiotechnology
  • Place of Presentation: Zhunan, Taiwan
• [Presentation] Invited speaker, 9th International Conference "Medical Applications of Novel Biomaterials and Nano-biotechnology" (2010)
  • Author(s): A.Maruyama
  • Organizer: DNA diagnostics using new cationic polymers
  • Place of Presentation: Montecatini Terme
• [Presentation] Caotionic Comb-type Copolymer as a Nucleic Acide Chaperone for DNA Quadrupiex (2009)
  • Author(s): 丸山厚
  • Organizer: The 6th International Symposium on Nucleic Acids Chemistry, 2009
  • Place of Presentation: 岐阜県高山市
  • Year and Date: 2009-09-30
• [Presentation] 高分子材料による核酸操作と遺伝子診断への展開 (2009)
  • Author(s): 丸山 厚
  • Organizer: 第59回医用高分子研究会
  • Place of Presentation: 東京工業大学
  • Year and Date: 2009-03-17
• [Presentation] 人工核酸シャペロン材料の設計と遺伝子多型解析への展開 (2009)
  • Author(s): 丸山 厚
  • Organizer: 東京大学ナノバイオ・インテグレーション研究拠点シンポジウム「ナノバイオセンシングの最前線」
  • Place of Presentation: 東京大学
  • Year and Date: 2009-03-04
• [Presentation] Invited speaker, International conference on materials for advanced technologies, "DNA Nanoscience and Biophysics" (2009)
  • Author(s): A.Maruyama
  • Organizer: Cationic Comb-type Copolymers as DNA Chaperones
  • Place of Presentation: Singapore
• [Presentation] Manipulation of DNA folding with soft interpolyelectrolyte complex (2008)
  • Author(s): Atsushi Maruyama
  • Organizer: 研究所(先導研・電子研・多元研)連携・SNAMS・CREST ジョイントミニ国際シンポジウム : エンジニアリング・ネオバイオミメティクスとソフトナノマテリアル
  • Place of Presentation: 東北大学
  • Year and Date: 2008-12-12
• [Presentation] Highly faithful DNA hybridization produced by an engineered folding pathway and cationic comb-type copolymers (2008)
  • Author(s): Atsushi Maruyama
  • Organizer: International symposium on gene delivery and biomaterials
  • Place of Presentation: 中国
  • Year and Date: 2008-11-27
• [Presentation] 塩基性ポリアミノ酸誘導体による核酸構造の動的制御と核酸ナノバイオヘの応用 (2008)
  • Author(s): 丸山 厚
  • Organizer: 第10回ペプチドフォーラム“協奏分子としてのアルギニン : 細胞・分子機能における普遍性・必然性とその応用"
  • Place of Presentation: 京都薬科大学
  • Year and Date: 2008-11-07
• [Presentation] 核酸フォールディング過程に着目した核酸配列認識の厳密化 (2008)
  • Author(s): 丸山 厚
  • Organizer: 九大先導研・北大電子研・東北大多元研 研究所間連携研究交流会
  • Place of Presentation: 帝人本社(東京)
  • Year and Date: 2008-10-30
• [Presentation] 高分子複合体による核酸構造の動的制御とナノバイオヘの展開 (2008)
  • Author(s): 丸山 厚
  • Organizer: ポストシリコン物質・デバイス創製基盤技術アライアンス「ナノ分子メカニクス・バイオメカニクス」研究グループ分科会
  • Place of Presentation: ホテル阪急エキスポパーク(大阪)
  • Year and Date: 2008-10-17
• [Presentation] Design of artificial DNA chaperone for DNA nanobiotechnology (2008)
  • Author(s): Atsushi Maruyama
  • Organizer: The 42th IUPAC World Polymer Congress (Macro 2008)
  • Place of Presentation: Taipei、Taiwan
  • Year and Date: 2008-07-02
• [Presentation] Cationic comb-type copolymer as an artificial nucleic acid chaperone : acceleration of DNA hybridization (2008)
  • Author(s): Atsushi Maruyama
  • Organizer: International Symposium on Polymer Chemistry
  • Place of Presentation: Hefei、China
  • Year and Date: 2008-06-18
• [Book] 核酸医薬の最前線(人工核酸シャペロンの設計とナノバイオテクノロジーへの展開)(和田猛監修) (2009)
  • Author(s): 丸山厚
  • Publisher: シーエムシー出版(分担執筆)
• [Book] バイオマテリアル-生体材料-(生体材料と核酸技術) (2008)
  • Author(s): 丸山厚
  • Publisher: (分担執筆)
• [Book] 次世代医療のための高分子材料工学(くし型高分子ナノ材料)(秋吉一成、岸田晶夫編) (2008)
  • Author(s): 丸山厚
  • Publisher: シーエムシー出版(分担執筆)
• [Book] 次世代医療のための高分子材料工学 (2008)
  • Author(s): 丸山厚 (分担執筆)
  • Total Pages: 286
  • Publisher: シーエムシー出版
• [Remarks] ホームページ
  • URL: http://www.cm.kyushu-u.ac.jp/wmaruyama/
• [Patent(Industrial Property Rights)] 温度PH及び塩濃度応答性材及びその用途 (2010)
  • Inventor(s): 崎田直彦, 丸山厚
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Number: 2010-066792
  • Filing Date: 2010-03-23