Therapeutic strategy of drug delivery systems utilizing unique tumor environment

2013 Fiscal Year Final Research Report

• Project/Area Number: 23240072
• 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: Kyoto University
• Principal Investigator: HASHIDA Mitsuru 京都大学, 薬学研究科(研究院), 教授 (20135594)
• Co-Investigator(Kenkyū-buntansha): YAMASHITA Fumiyoshi 京都大学, 薬学研究科, 准教授 (30243041)
• Co-Investigator(Renkei-kenkyūsha): KAWAKAMI Shigeru 長崎大学, 医歯薬学総合研究科, 教授 (20322307) ; HIGUCHI Yuriko 京都大学, 健康長寿社会の総合医療開発ユニット, 講師 (40402797) ; HASHIDA Yasuhiko 京都大学, 物質-細胞統合システム拠点, 特定研究員 (30512462)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: ドラッグデリバリー / 核酸医療 / がん治療 / 免疫活性化 / 小胞体ストレス / ナノバイオ材料 / 超音波医科学

Research Abstract

Cancer cells establish tumor environment that allows them to resist stressful conditions such as low oxygen and low nutrients and escape host immune responses. The present investigation aimed at developing innovative anti-cancer therapeutic systems with paying attention to the unique characteristics of tumorous tissues from those of normal tissues. To achieve this goal, we focused on nucleic acid drugs with high specificity that can break the resistance systems in cancer, and developed effective delivery systems for the drugs to the target by combination of physical and chemical means.

Research Products

• [Journal Article] In vitro evaluation of inhibitory effect of nuclear factor-kappaB activity by small interfering RNA on pro-tumor characteristics of M2-like macrophages (2014)
  • Author(s): Y. Kono, S. Kawakami, Y. Higuchi, F. Yamashita, M. Hashida
  • Journal Title: Biol. Pharm. Bull Volume: 37(1) Pages: 137-144
  • DOI: 10.1248/bpb.b13-00659
  • Peer Reviewed
• [Journal Article] Inhibition of cancer gell growth by GRP78 siRNA lipoplex via activation of unfolded protein response (2014)
  • Author(s): K. Matsumura, C. Sakai, S. Kawakami, F. Yamashita, M. Hashida
  • Journal Title: Biol. Pharm. Bull Volume: 37(4) Pages: 648-653
  • DOI: 10.1248/bpb.b13-00930
  • Peer Reviewed
• [Journal Article] Tumour-associated macrophages targeted transfection with NF-kappaB decoy/mannose-modified bubble lipoplexes inhibits tumour growth in tumour-bearing mice (2014)
  • Author(s): Y. Kono, S. Kawakami, Y. Higuchi, F. Yamashita, M. Hashida
  • Journal Title: J. Drug Targeting Volume: (in press)
  • DOI: 10.3109/1061186x.2014.880443
  • Peer Reviewed
• [Journal Article] Pivotal role of oxidative stress in tumor metastasis under diabetic conditions in mice (2013)
  • Author(s): M. Ikemura, M. Nishikawa, K. Kusamori, M. Fukuoka, F. Yamashita, M. Hashida
  • Journal Title: J. Controlled Release Volume: 170(2) Pages: 191-197
  • DOI: 10.1016/j.jconrel.2013.05.028
  • Peer Reviewed
• [Journal Article] The involvement of NK cells activation following intranasal administration of CpG DNA lipoplex in the prevention of pulmonary metastasis and peritoneal dissemination in mice (2012)
  • Author(s): S. Zhou, S. Kawakami, Y. Higuchi, F. Yamashita, M. Hashida
  • Journal Title: Clin. Exp. Metastasis Volume: 29 Pages: 63-70
  • DOI: 10.1007/s10585-011-9429-1
  • Peer Reviewed
• [Journal Article] Enhancement of gene expression by transcriptional activation using doxorubicin-loaded liposome/pDNA complexes (2012)
  • Author(s): K. Un, Y. Kono, F. Yamashita, S. Kawakami, M.Hashida
  • Journal Title: Pharmazie Volume: 67(5) Pages: 400-405
  • DOI: 10.1691/ph.2012.1702
  • Peer Reviewed
• [Journal Article] Efficient suppression of ICAM-1 using ultrasound-responsive and mannose-modified lipoplexes inhibits acute hepatic inflammation (2012)
  • Author(s): K. Un, S. Kawakami, M. Yoshida, Y. Higuchi, R. Suzuki, K. Maruyama, F. Yamashita, M.Hashida
  • Journal Title: Hepatology Volume: 56(1) Pages: 259-269
  • DOI: 10.1002/hep.25607
  • Peer Reviewed
• [Journal Article] Creation of pure nanodrugs and their anticancer properties (2012)
  • Author(s): H. Kasai, T. Murakami, Y. Ikuta, Y. Koseki, K. Baba, H. Oikawa, H. Nakanishi, M. Okada, M. Shoji, M. Ueda, H. Imahori, M. Hashida
  • Journal Title: Angew. Chem. Int. Ed Volume: 51 Pages: 10315-10318
  • DOI: 10.1002/anie.201204596
  • Peer Reviewed
• [Presentation] マンノース修飾バブルリポソームを用いたNF-kappaB 活性制御による腫瘍関連マクロファージのphenotype 変化 (2013)
  • Author(s): 河野裕允、川上 茂、樋口ゆり子、鈴木 亮、丸山一雄、山下富義、橋田 充
  • Organizer: 日本薬剤学会第28年会
  • Place of Presentation: ウインクあいち(愛知県)
  • Year and Date: 20130523-25
• [Presentation] Ultrasound triggered doxorubicin loaded microbubbles for effective therapeutic outcomes in melanoma (2013)
  • Author(s): R. Abdalkader, M. Hashida, S. Kawakami, R. Suzuki, K. Maruyama
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2013-10-04
• [Presentation] Inhibition of tumor growth by NF-κ B decoy transfection into TAM using mannose-modified bubble lipoplexes in mice (2013)
  • Author(s): 河野裕允、川上 茂、鈴木 亮、丸山一雄、橋田 充
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2013-10-04
• [Presentation] NF-kB を標的とする抑制性オリゴ核酸による癌微小環境中のマクロファージの免疫再賦活化 (2012)
  • Author(s): 河野裕允、川上 茂、樋口ゆり子、山下富義、橋田 充
  • Place of Presentation: 仙台市民会館(宮城県)
  • Year and Date: 20120624-26
• [Presentation] New Drug Delivery Systems (2012)
  • Author(s): M. Hashida
  • Organizer: 3rd International Regulatory Workshop on A to Z on Bioequivalence
  • Place of Presentation: The Hungarian Academy of Sciences, Budapest, Hungary
  • Year and Date: 20120604-06
• [Presentation] GRP78 siRNAリポプレックスによるがん細胞アポトーシスの誘導と抗がん剤耐性の克服 (2012)
  • Author(s): 松村一史、川上 茂、山下富義、橋田 充
  • Organizer: 日本薬学会第132回年会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2012-03-30