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siRNA delivery to tumor by sequential injection of anionic polymer and siRNA lipoplex

Research Project

Project/Area Number 26460046
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionHoshi University

Principal Investigator

Hattori Yoshiyuki  星薬科大学, 薬学部, 准教授 (90350222)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordssiRNA / リポソーム / 肝転移がん / コンドロイチン硫酸 / 負電荷ポリマー / protein kinase N3 / ヒト乳がん / がん治療 / リポプレックス / 正電荷リポプレックス / ポリグルタミン酸 / がん
Outline of Final Research Achievements

We developed novel siRNA transfer method to the liver by sequential intravenous injection of anionic polymer and cationic liposome/siRNA complex (siRNA lipoplex). When siRNA lipoplex was intravenously injected into mice bearing liver metastasis, the accumulation of siRNA was mainly observed in the lungs. In contrast, when siRNA lipoplex was intravenously injected into mice bearing liver metastasis immediately after intravenous injection of chondroitin sulfate (CS), siRNA was accumulated in tumor-metastasized liver. In terms of a gene silencing effect, sequential injections of CS plus siRNA lipoplex could reduce expression of target gene in liver metastasis. Moreover, sequential injections of CS plus siRNA lipoplex of protein kinase N3 (PKN3) siRNA could suppress tumor growth in the mice bearing liver metastasis. From these findings, sequential injection of CS and siRNA lipoplex might be a novel systemic method of delivering siRNA to liver metastasis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (30 results)

All 2017 2016 2015 2014 Other

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 7 results,  Open Access: 3 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Therapeutic effects of protein kinase N3 small interfering RNA and doxorubicin combination therapy on liver and lung metastases2017

    • Author(s)
      Y. Hattori, T. Kikuchi, M. Nakamura, K. Ozaki, H. Onishi
    • Journal Title

      Oncol. Lett.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Small interfering RNA delivery into the liver by cationic cholesterol derivative-based liposomes2017

    • Author(s)
      Y. Hattori, Y. Machida, M. Honda, N. Takeuchi, Y. Yoshiike, H. Ohno, H. Onishi
    • Journal Title

      J. liposome Res.

      Volume: 印刷中 Issue: 4 Pages: 264-273

    • DOI

      10.1080/08982104.2016.1205599

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of injection route of anionic polymer for siRNA delivery into the liver by sequential injection of anionic polymer and cationic lipoplex of siRNA2016

    • Author(s)
      Y. Hattori, Y. Yoshiike, T. Kikuchi, N. Yamamoto, K. Ozaki, H. Onishi
    • Journal Title

      J. Drug Deliv. Sci. Tec.

      Volume: 35 Pages: 40-49

    • DOI

      10.1016/j.jddst.2016.05.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Delivery of plasmid DNA into tumors by intravenous injection of PEGylated cationic lipoplexes into tumor-bearing mice2016

    • Author(s)
      Y. Hattori
    • Journal Title

      Pharmacology & Pharmacy

      Volume: 7 (7) Issue: 07 Pages: 272-282

    • DOI

      10.4236/pp.2016.77034

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic effect for liver-metastasized tumor by sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA2016

    • Author(s)
      Y. Hattori, S. Arai, T. Kikuchi, K. Ozaki, K. Kawano, E. Yonemochi
    • Journal Title

      Journal of Drug Targeting

      Volume: 24 (4) Issue: 4 Pages: 309-317

    • DOI

      10.3109/1061186x.2015.1070856

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] siRNA delivery to lung-metastasized tumor by systemic injection with cationic liposome2015

    • Author(s)
      Y. Hattori, A. Nakamura, S. Arai, K. Kawano, Y. Maitani, E. Yonemochi
    • Journal Title

      Journal of Liposome Research

      Volume: 25 (4) Issue: 4 Pages: 279-286

    • DOI

      10.3109/08982104.2014.992024

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Optimization of siRNA delivery method into the liver by sequential injection of polyglutamic acid and cationic lipoplex2015

    • Author(s)
      Y. Hattori, S. Arai, T. Kikuchi, M. Hamada, R. Okamoto, Y. Machida and K. Kawano
    • Journal Title

      Pharmacology & Pharmacy

      Volume: 6 (7) Issue: 07 Pages: 302-310

    • DOI

      10.4236/pp.2015.67032

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] siRNA Delivery into Tumor Cells by Cationic Cholesterol Derivative-Based Nanoparticles and Liposomes2015

    • Author(s)
      Y. Hattori, E. Hara, Y. Shingu, D. Minamiguchi, A. Nakamura, S. Arai, H. Ohno, K. Kawano, N. Fujii, E. Yonemochi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Issue: 1 Pages: 30-38

    • DOI

      10.1248/bpb.b14-00526

    • NAID

      130004872237

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA could effectively deliver siRNA to the liver2014

    • Author(s)
      Y. Hattori, S. Arai, R. Okamoto, M. Hamada, K. Kawano, E. Yonemochi
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 476 Issue: 1-2 Pages: 289-298

    • DOI

      10.1016/j.ijpharm.2014.09.059

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] コンドロイチン硫酸とsiRNAリポプレックスの連続投与におけるコンドロイチン硫酸が及ぼすsiRNAの生体内分布への影響2017

    • Author(s)
      服部喜之,花屋志織,吉池悠貴,菊地拓人,大西啓
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of siRNA delivery system to liver metastasis for therapeutic application2016

    • Author(s)
      Yoshiyuki Hattori
    • Organizer
      The 2016 Mogan Mountain International Summit on Green Pharmaceuticals
    • Place of Presentation
      中国・浙江省・杭州市
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PKN3 siRNAリポプレックスとドキソルビシンの併用療法による肝ならびに肺転移乳がんに対する抗腫瘍効果の検討2016

    • Author(s)
      菊地拓人,服部喜之,中村麻里,尾﨑惠一,大西啓
    • Organizer
      第32回日本DDS学会学術集会
    • Place of Presentation
      静岡
    • Year and Date
      2016-06-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 負電荷ポリマーとsiRNAリポプレックス連続投与による肝臓へのsiRNA送達における負電荷ポリマーの種類と投与法の検討2016

    • Author(s)
      菊地拓人,服部喜之,吉池悠貴,山本菜摘,尾﨑惠一,大西啓
    • Organizer
      日本薬剤学会 第31年会
    • Place of Presentation
      岐阜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] PKN3 siRNAリポプレックスとドキソルビシンの併用療法による肝転移乳がんに対する抗腫瘍効果の検討2016

    • Author(s)
      服部喜之,菊地拓人,大西啓
    • Organizer
      遺伝子・デリバリー研究会 第16回シンポジウム
    • Place of Presentation
      神奈川
    • Year and Date
      2016-05-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] コンドロイチン硫酸とsiRNAリポプレックスの連続投与による肝臓へのsiRNAの導入における投与法の検討2016

    • Author(s)
      吉池悠貴,服部喜之,菊地拓人,大西啓
    • Organizer
      遺伝子・デリバリー研究会 第16回シンポジウム
    • Place of Presentation
      神奈川
    • Year and Date
      2016-05-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] PKN3 siRNAリポプレックスとドキソルビシンの併用療法による肺転移がんに対する治療効果2016

    • Author(s)
      中村麻里,服部喜之,菊地拓人,大西啓
    • Organizer
      遺伝子・デリバリー研究会 第16回シンポジウム
    • Place of Presentation
      神奈川
    • Year and Date
      2016-05-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] コンドロイチン硫酸とsiRNAリポプレックスの連続投与とドキソルビシンの併用療法による肝転移がんに対する抗腫瘍効果の検討2016

    • Author(s)
      菊地拓人, 服部喜之, 大西啓
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] コンドロイチン硫酸とsiRNAリポプレックスの連続投与後のsiRNAの生体内分布に及ぼすコンドロイチン硫酸の投与方法の検討2016

    • Author(s)
      吉池悠貴, 服部喜之, 菊地拓人, 大西啓
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] ポリグルタミン酸と正電荷リポプレックスの連続投与による肝臓へのsiRNA送達2015

    • Author(s)
      菊地拓人,服部喜之,新井翔平,町田曜子,濱田めぐみ,岡本遼,川野久美,米持悦生
    • Organizer
      第31回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 負電荷ポリマーとsiRNAリポプレックスの連続投与による肝転移がんに対する抗腫瘍効果と安全性評価2015

    • Author(s)
      服部喜之,新井翔平,川野久美
    • Organizer
      遺伝子・デリバリー研究会 第15回シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2015-05-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 負電荷ポリマーとsiRNAリポプレックスの連続投与による肝転移がんに対する遺伝子発現抑制効果と抗腫瘍効果2015

    • Author(s)
      服部喜之,新井翔平,川野久美,米持悦生
    • Organizer
      日本薬学会 第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] コンドロイチン硫酸と正電荷リポプレックスの連続投与による肝臓ならびに肝臓転移がんに対するsiRNA送達2014

    • Author(s)
      新井翔平,服部喜之,川野久美,米持悦生
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2014
    • Place of Presentation
      東京
    • Year and Date
      2014-09-08 – 2014-09-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA could effectively deliver siRNA to the liver2014

    • Author(s)
      Y. Hattori, S. Arai, R. Okamoto, M. Hamada, K. Kawano and E. Yonemochi
    • Organizer
      Liposome Research Days 2014
    • Place of Presentation
      デンマーク,コッペンハーゲン
    • Year and Date
      2014-08-04 – 2014-08-07
    • Related Report
      2014 Research-status Report
  • [Presentation] ポリグルタミン酸と正電荷リポプレックスの連続投与は肝臓ならびに肝臓転移がんに対してsiRNAによる遺伝子発現抑制を誘導する2014

    • Author(s)
      新井翔平、服部喜之、岡本遼、濱田めぐみ、川野久美、米持悦生
    • Organizer
      第30回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-30 – 2014-07-31
    • Related Report
      2014 Research-status Report
  • [Presentation] 負電荷ポリマーと正電荷リポプレックスの連続投与による肝臓へのsiRNA送達における負電荷ポリマーの種類と正電荷リポプレックスの荷電比の最適化2014

    • Author(s)
      岡本 遼、服部喜之、新井翔平、濱田めぐみ、川野久美、米持悦生
    • Organizer
      第30回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-30 – 2014-07-31
    • Related Report
      2014 Research-status Report
  • [Presentation] 負電荷ポリマー被覆リポプレックスによる肝臓へのsiRNA送達2014

    • Author(s)
      服部喜之、西垣磨優、大倉博之、中村文子、新井翔平、川野久美、米持悦生
    • Organizer
      日本薬剤学会 第29年会
    • Place of Presentation
      埼玉
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 肝臓へsiRNAを送達するための負電荷ポリマー溶液と正電荷リポプレックスの連続投与法の開発2014

    • Author(s)
      新井翔平、服部喜之、岡本遼、濱田めぐみ、川野久美、米持悦生
    • Organizer
      日本薬剤学会 第29年会
    • Place of Presentation
      埼玉
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Research-status Report
  • [Remarks] 星薬科大学 医療薬剤学教室 服部喜之

    • URL

      http://polaris.hoshi.ac.jp/kyoshitsu/iryouyakuzai/hattori.htm

    • Related Report
      2016 Annual Research Report
  • [Remarks] 星薬科大学 医療薬剤学教室

    • URL

      http://polaris.hoshi.ac.jp/kyoshitsu/iryouyakuzai/DDR%28J%29%20top-page.htm

    • Related Report
      2015 Research-status Report
  • [Remarks] 星薬科大学 医療薬剤学教室

    • URL

      http://www.hoshi.ac.jp/site/kyoiku/kyoushitsuhgaid/13kyoushitsu.iryouyakuzai.php

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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