Development of nano medicine for anti-bladder cancer based on human immunology

• Project/Area Number: 26713002
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: NAKAMURA Takashi 北海道大学, 薬学研究科(研究院), 助教 (20604458)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000); Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2014: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 膀胱がん / BCG / ナノ粒子 / がん免疫療法 / ヒト免疫学 / リポソーム / 網羅的遺伝子解析 / 薬物送達学 / ドラッグデリバリー / 網羅的遺伝子発現解析

Outline of Final Research Achievements

The purpose of this study is to develop a nanoparticle system achieving live BCG mediated antitumor effects against bladder cancer. We successfully found that the modification of PEGylated lipid into nanoparticles efficiently inhibited the aggregation of nanoparticle in human urine. We also developed the novel nanoparticle for efficient siRNA delivery to immune cells. The internalization of BCG cell wall skeleton in bladder cancer cells is essential for induction of antitumor effect. Moreover, we found key cytokines associated with antitumor effect of BCG by analyses with microarray and qRT-PCR. We currently progress selection of BCG components and development of Nano-BCG.

Research Products

• [Journal Article] Innovative technologies in Nanomedicines: from passive targeting to active targeting/from controlled pharmacokinetics to controlled intracellular pharmacokinetics. (2017)
  • Author(s): Sato Y, Sakurai Y, Kajimoto K, Nakamura T, Yamada Y, Akita H, Harashima H.
  • Journal Title: Macromolecular Bioscience Volume: 17 Issue: 1 Pages: 1-16
  • DOI: 10.1002/mabi.201600179
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Modifying Cationic Liposomes with Cholesteryl-PEG Prevents Their Aggregation in Human Urine and Enhances Cellular Uptake by Bladder Cancer Cells (2017)
  • Author(s): Takashi Nakamura, Yosuke Noma, Yu Sakurai, Hideyoshi Harashima
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 2 Pages: 234-237
  • DOI: 10.1248/bpb.b16-00770
  • NAID: 130005308415
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of a Drug Delivery System for Cancer Immunotherapy (2016)
  • Author(s): Takashi Nakamura
  • Journal Title: YAKUGAKU ZASSHI Volume: 136 Issue: 11 Pages: 1477-1484
  • DOI: 10.1248/yakushi.16-00187
  • NAID: 130005267659
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2016-11-01
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of a multifunctional envelope-type nano device and its application to nanomedicine. (2016)
  • Author(s): Sato Y, Nakamura T, Yamada Y, Harashima H.
  • Journal Title: J Control Release Volume: 244 Pages: 194-204
  • DOI: 10.1016/j.jconrel.2016.06.042
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines (2016)
  • Author(s): Takashi Nakamura, Moeka Kuroi, Yuki Fujiwara, Shota Warashina, Yusuke Sato, Hideyoshi Harashima
  • Journal Title: Scientific Reports Volume: 6 Issue: 1
  • DOI: 10.1038/srep37849
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells. (2016)
  • Author(s): Warashina S, Nakamura T, Sato Y, Fujiwara Y, Hyodo M, Hatakeyama H, Harashima H
  • Journal Title: J Control Release. Volume: 225 Pages: 183-191
  • DOI: 10.1016/j.jconrel.2016.01.042
  • NAID: 120005981350
  • Peer Reviewed
• [Journal Article] Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model (2014)
  • Author(s): Takashi Nakamura, Masafumi Fukiage, Yoshiteru Suzuki, Ikuya Yano, Jun Miyazaki, Hiroyuki Nishiyama, Hideyuki Akaza, Hideyoshi Harashima
  • Journal Title: Journal of Controlled Release Volume: 196 Pages: 161-167
  • DOI: 10.1016/j.jconrel.2014.10.007
  • NAID: 120005537473
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 脂質ナノ粒子を用いたヒト免疫細胞株への効率的siRNA導入 (2016)
  • Author(s): 中村孝司、黒井萌花、藤原優希、藁科翔太、佐藤悠介、原島秀吉
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: グランシップ（静岡県・静岡市）
  • Year and Date: 2016-06-30
• [Presentation] ナノテクノロジーで制御するがんアジュバントシステムの創製 (2016)
  • Author(s): 中村孝司
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 長良川国際会議場・岐阜都ホテル（岐阜県・岐阜市）
  • Year and Date: 2016-05-19
  • Invited
• [Presentation] 樹状細胞への効率的siRNAデリバリーシステムの開発 (2015)
  • Author(s): 中村孝司、藁科翔太、佐藤悠介、兵藤守、畠山浩人、原島秀吉
  • Organizer: 日本薬剤学会第30年会
  • Place of Presentation: 長崎ブリックホール・長崎新聞文化ホール（長崎県長崎市）
  • Year and Date: 2015-05-21
• [Presentation] がん免疫療法を促進するDrug Delivery Systemの開発 (2015)
  • Author(s): 中村孝司
  • Organizer: 日本薬学会北海道支部第142回例会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-05-16
  • Invited
• [Presentation] BCG-CWS搭載ナノ粒子を用いた膀胱がん免疫療法剤の開発 (2015)
  • Author(s): 中村孝司、吹上雅文、鈴木嘉晃、矢野郁也、宮崎淳、西山博之、赤座英之、中山俊憲、原島秀吉
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸 神戸学院大学 兵庫医療大学
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 免疫応答の増強を可能とするエンドソーム脱出促進型siRNAナノキャリアの開発 (2014)
  • Author(s): 藁科翔太、中村孝司、佐藤悠介、兵藤守、畠山浩人、原島秀吉
  • Organizer: 第36回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 徳島 徳島大学
  • Year and Date: 2014-11-20 – 2014-11-21
• [Remarks] 北海道大学大学院薬学研究院 薬剤分子設計学研究室ホームページ
  • URL: http://www.pharm.hokudai.ac.jp/yakusetu/index.html
• [Remarks] 薬剤分子設計学研究室ホームページ
  • URL: http://www.pharm.hokudai.ac.jp/yakusetu/index.html