Development of poorly water-soluble drug encapsulated protein nanocapsule possessing cancer directivity and application to DDS

2015 Fiscal Year Final Research Report

• Project/Area Number: 25242046
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Osaka Prefecture University
• Principal Investigator: Inui Takashi 大阪府立大学, 生命環境科学研究科(系), 教授 (80352912)
• Co-Investigator(Kenkyū-buntansha): ISHIBASHI Osamu 大阪府立大学, 生命環境科学研究科, 准教授 (70293214) ; KATAOKA Yosuke 理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (40291033) ; DOI Hisashi 理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (00421818)
• Co-Investigator(Renkei-kenkyūsha): NAKAJIMA Hidemitsu 大阪府立大学, 生命環境科学研究科, 准教授 (30405360)
• Research Collaborator: WADA Koichi ; YAGI Naoto ; KIDA Tatsuya
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: DDS / 難水溶性薬剤 / タンパク質ナノカプセル / 癌指向性 / 生体内輸送蛋白質

Outline of Final Research Achievements

We introduced CRGDK peptide, a tumor recognition peptide, at a C-terminal region of lipocalin-type prostaglandin D synthase (L-PGDS). L-PGDS-CRGDK labeled with a fluorescent reagent Cyto 750 was administered intravenously to human prostate cancer cells-bearing nude mice, and the metabolic disposition of L-PGDS-CRGDK was investigated using in vivo imaging system, resulting that a transient accumulation of L-PGDS-CRGDK to the cancer tissues was observed after 30 min to 5 h of the administration. Futhermore, we generated L-PGDS-based redox sensitive protein capsules by introducing a disulfide bond into the upper part of the drug-binding cavity of L-PGDS. The disulfide bond in capsules was opened and closed in an oxidation-reduction environment, suggesting that the capsules could be used as a drug delivery vehicle with drug controlled-release property.

Free Research Field

蛋白質科学、薬理学、構造生物学、生化学