Development of innovative drug delivery carrier targeting tumor microenvironment and application for intractable cancer
| Project/Area Number |
17K15511
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
Hitoshi Maeda 熊本大学, 大学院生命科学研究部(薬), 助教 (80791483)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | がん微小環境 / 腫瘍間質 / マクロファージ / 線維芽細胞 / アルブミン / ポリエチレングリコール / ドラッグデリバリーシステム / 腫瘍関連マクロファージ / 癌関連線維芽細胞 / 薬学 |
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| Outline of Final Research Achievements |
The tumor microenvironment including stromal cells forms an abominable tumor-promoting network. Stromal cells are divisible into tumor-associated macrophage (TAM) and cancer-associated fibroblast (CAF), both of which express mannose receptors, CD206 and CD280, respectively. We have developed mannosylated human serum albumin (Man-HSA) that has a potential to deliver therapeutics to cells expressed mannose receptors. However, Man-HSA is not suitable for cancer-targeting carrier due to own hepatic distribution. Herein, we focused on the polyethylene glycol (PEG) and developed cancer stromal-targeting carrier, Mono-PEGylated Man-HSA. Through own PEG and sugar chain, Mono-PEGylated Man-HSA preferentially distributed to tumor tissue and recognized TAM and CAF. These stromal cells and extracellular matrix are remarkably disrupted by complex of Mono-PEGylated Man-HSA with paclitaxel. The current study suggests the potential of Mono-PEGylated Man-HSA for the treatment of intractable cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、モノクローナル抗体医薬をはじめとする分子標的医薬の台頭によりこれまでの低分子有機化合物を中心とした抗がん剤開発から転換期を迎えている。一方で、抗体の生産コストの問題から医療費の高騰が世界的に問題となっており、抗体を用いず低分子・中分子を腫瘍特異的に作用させる技術が望まれる。本発明で用いる薬剤担体は、低分子・中分子と容易に結合させることが可能であり、腫瘍微小環境に存在するTAM/CAFを標的とすることで腫瘍特異的に効率よく抗癌剤を送達することが可能である。さらに本発明は、全世界で抗がん剤開発を行っている企業に対し提供可能な基盤技術であり、技術開示を進め連携・臨床応用を図っていく計画である。
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Repeated Administration of Kupffer Cells-Targeting Nanoantioxidant Ameliorates Liver Fibrosis in an Experimental Mouse Model2020
Author(s)
Maeda H, Minayoshi Y, Ichimizu S, Mizuta Y, Nagasaki T, Matsusaka K, Oshiro S, Oniki K, Saruwatari J, Ishima Y, Watanabe H, Otagiri M, Maruyama T.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 43
Issue: 1
Pages: 93-101
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2020-01-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic Fusion of Type-I Interferon to a Recombinant Albumin Mutant with polymannosylated N-linked oligosaccharide attached is a Novel and Superior Kupffer Cell Targeting Agent for the Treatment of Hepatitis.2018
Author(s)
Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, Kinoshita R, Enoki Y, Imafuku T, Chuang VTG, Koga T, Fujiwara Y, Takeya M, Sonoda K, Wakayama T, Taguchi K, Ishima Y, Ishida T, Iwakiri Y, Tanaka M, Sasaki Y, Watanabe H, Otagiri M, Maruyama T.
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Journal Title
Drug Delivery
Volume: 25
Issue: 1
Pages: 1067-1077
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery.2018
Author(s)
Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Nakamura Y, Chuang VTG, Kinoshita R, Nishida K, Tanaka R, Enoki Y, Ishima Y, Kuniyasu A, Kobashigawa Y, Morioka H, Futaki S, Otagiri M, Maruyama T.
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Journal Title
J Control Release.
Volume: 10;277
Pages: 23-34
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Dual Therapeutic Effects of an Albumin-Based Nitric Oxide Donor on 2 Experimental Models of Chronic Kidney Disease.2018
Author(s)
Oshiro S, Ishima Y, Maeda H, Honda N, Bi J, Kinoshita R, Ikeda M, Iwao Y, Imafuku T, Nishida K, Miyamura S, Watanabe H, Otagiri M, Maruyama T.
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Journal Title
J Pharm Sci.
Volume: 107(3)
Pages: 848-855
Related Report
Peer Reviewed
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[Journal Article] Development of Kupffer Cell Targeting Type-Ⅰ Interferon for the Treatment of Hepatitis via Inducing Anti-inflammatory and Immunomodulatory Actions2018
Author(s)
Minayoshi Y, Maeda H, Yanagisawa H, Sonoda K, Wakayama T, Hamasaki K, Mizuta Y, Nishida K, Kinoshita R, Enoki Y, Chuang VTG, Koga T, Fujiwara Y, Takeya M, Taguchi K, Ishima Y , Ishida T, Iwakiri Y, Tanaka M, Sasaki Y, Watanabe H, Otagiri M, Maruyama T
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Journal Title
Drug Delivery
Volume: 印刷中
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Parathyroid hormone contributes to the down-regulation of cytochrome P450 3A through the cAMP/PI3K/PKC/PKA/NF-κB signaling pathway in secondary hyperparathyroidism.2017
Author(s)
Watanabe H, Sugimoto R, Ikegami K, Enoki Y, Imafuku T, Fujimura R, Bi J, Nishida K, Sakaguchi Y, Murata M, Maeda H, Hirata K, Jingami S, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Maruyama T.
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Journal Title
Biochem Pharmacol.
Volume: 1;145
Pages: 192-201
Related Report
Peer Reviewed / Open Access
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