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Development of siRNA therapy for liver-metastasized tumor by sequential intravenous injection of chondroitin sulfate and siRNA lipoplex

Research Project

Project/Area Number 17K08251
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, 教授 (90350222)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordssiRNA / 正電荷リポソーム / がん治療 / 肝転移がん / コンドロイチン硫酸 / 転移がん / リポソーム / DDS
Outline of Final Research Achievements

Previously, we found that intravenous injection of chondroitin sulfate (CS), followed by intravenous injection of cationic liposome/siRNA complex (siRNA lipoplex) could deliver siRNA into the liver metastasis. In this study, we examined the effects of the type of cationic lipid in the liposome on siRNA delivery into the liver and liver metastasis. We prepared 17 types of cationic liposomes to evaluate the gene-silencing effect of siRNA in mouse liver following sequential injection of CS plus siRNA lipoplex. In 14 types of cationic liposomes, siRNA was accumulated in the liver when siRNA lipoplexes were injected immediately after CS. However, suppression of targeted mRNA expression in the liver after sequential injection of CS plus siRNA lipoplex were observed in only 3 types of cationic liposomes. Furthermore, sequential injection of PKL1 siRNA or HSF1 siRNA lipoplexes into mice with liver HeLa metastasis could suppress tumor growth.

Academic Significance and Societal Importance of the Research Achievements

短鎖二本鎖RNA (siRNA)は、配列特異的に遺伝子の発現を抑制できることから、siRNAを利用した肝転移がんなどの難治性疾患に対する創薬開発が期待されているが、標的組織にsiRNAを送達することが困難であった。そこで肝転移がんに対するsiRNAの送達法として、siRNAと正電荷リポソームの複合体(siRNAリポプレックス)投与直前にコンドロイチン硫酸を投与する連続投与法を開発し、連続投与に用いる正電荷リポソーム製剤の正電荷脂質の違いによりsiRNAの効果が異なることを明らかにした。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 Other

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (8 results) Remarks (3 results)

  • [Journal Article] Effect of cationic lipid in cationic liposomes on siRNA delivery into the lung by intravenous injection of cationic lipoplex.2019

    • Author(s)
      Hattori Y, Nakamura M, Takeuchi N, Tamaki K, Shimizu S, Yoshiike, Y, Taguchi M, Ohno H, Ozaki K, Onishi H.
    • Journal Title

      J. Drug Target.

      Volume: 27 Issue: 2 Pages: 217-227

    • DOI

      10.1080/1061186x.2018.1502775

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimized combination of cationic lipids and neutral helper lipids in cationic liposomes for siRNA delivery into the lung by intravenous injection of siRNA lipoplexes.2019

    • Author(s)
      Hattori Y, Tamaki K, Ozaki K, Kawano K, Onishi H.
    • Journal Title

      J. Drug Deliv. Sci. Tec.

      Volume: 52 Pages: 1042-1050

    • DOI

      10.1016/j.jddst.2019.06.016

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of cationic lipid type in cationic liposomes for siRNA delivery into the liver by sequential injection of chondroitin sulfate and cationic lipoplex2018

    • Author(s)
      Y. Hattori, N. Takeuchi, M. Nakamura, Y. Yoshiike, M. Taguchi, H. Ohno, K. Ozaki, H. Onishi,
    • Journal Title

      Journal of Drug Delivery Science and Technology

      Volume: 48 Pages: 235-244

    • DOI

      10.1016/j.jddst.2018.09.022

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of in vitro and in vivo therapeutic anti-tumor efficacy of transduction of polo-like kinase 1 and heat shock transcription factor 1 small interfering RNA2017

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

      Experimental and Therapeutic Medicine

      Volume: 14 Pages: 4300-4306

    • DOI

      10.3892/etm.2017.5060

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of chondroitin sulfate on siRNA biodistribution and gene silencing effect in mice after injection of siRNA lipoplexes2017

    • Author(s)
      Y. Hattori, A. Nakamura, S. Hanaya, Y. Miyanabe, Y. Yoshiike, T. Kikuchi, K. Ozaki, H. Onishi
    • Journal Title

      Journal of Drug Delivery Science and Technology

      Volume: 41 Pages: 401-409

    • DOI

      10.1016/j.jddst.2017.08.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Progress in the development of lipoplex and polyplex modified with anionic polymer for efficient gene delivery2017

    • Author(s)
      Y. Hattori
    • Journal Title

      Journal of Genetic Medicine and Gene Therapy

      Volume: 1 Pages: 3-18

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] siRNA送達用正電荷リポソーム製剤に用いる正電荷脂質と中性脂質の最適化2019

    • Author(s)
      岸本準,大西啓,服部喜之
    • Organizer
      第63回日本薬学会関東支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] コンドロイチン硫酸とPLK1またはHSF1 siRNAリポプレックスの連続投与による肝転移がん治療2018

    • Author(s)
      服部喜之,菊地拓人,尾﨑惠一,大西啓
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 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におけるsiRNAの生体内分布と遺伝子発現抑制効果に及ぼす正電荷リポソームの正電荷脂質の影響2018

    • Author(s)
      服部喜之,中村麻里,竹内のぞみ,吉池悠貴,田口将光,大野浩章,尾﨑惠一,大西啓
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] コンドロイチン硫酸とsiRNAリポプレックス連続投与後のマウス肝臓におけるsiRNAの集積性の検討2017

    • Author(s)
      服部喜之,花屋志織,宮鍋侑大,中村文子,尾﨑惠一,大西啓
    • Organizer
      第17回遺伝子・デリバリー研究会シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 正電荷リポソームの正電荷脂質の違いによるsiRNAの遺伝子発現抑制効果およびマウス静注後のsiRNAの生体内分布への影響2017

    • Author(s)
      服部喜之,竹内のぞみ,中村麻里,大西啓
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 正電荷コレステロール誘導体を用いて調製したリポソーム製剤による肝臓へのsiRNA送達2017

    • Author(s)
      竹内のぞみ,服部喜之,五十嵐康晃,梅木優子,大西啓
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] コンドロイチン硫酸被覆siRNAリポプレックス投与とコンドロイチン硫酸とsiRNAリポプレックス連続投与による肝臓へのsiRNA送達性の比較2017

    • Author(s)
      服部喜之,吉池悠貴,大西啓
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] コンドロイチン硫酸とsiRNAリポプレックス連続投与における正電荷リポソームの正電荷脂質の違いによるsiRNAの生体内分布への影響2017

    • Author(s)
      中村麻里,服部喜之,設楽亮介,御園宥江,大西 啓
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Research-status Report
  • [Remarks] 星薬科大学 分子薬剤学研究室

    • URL

      https://polaris.hoshi.ac.jp/kyoshitsu/yakuzai/Pharmaceutics%20top-page.htm

    • Related Report
      2019 Annual Research Report
  • [Remarks] 星薬科大学 医療薬剤学研究室

    • URL

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

    • Related Report
      2018 Research-status Report
  • [Remarks] 星薬科大学 医療薬剤学研究室 ホームページ

    • URL

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

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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