Molecular Targeting Therapy with Intelligent Drug Delivery System using Transporter

利用转运蛋白的智能给药系统进行分子靶向治疗

• 批准号: 13557104
• 负责人: YANAGIE Hironobu
• 金额: $ 8.96万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557104/
• 关键词: Transporter; Anticancer resistant gene; DNA Microarray; Molecular targeting therapy; Anionic Polyethylene glycol; JTS-1; Drug Delivery System; Transfferin binding PEG-Liposome; 分子標的治療; ドラッグデリバリーシステム; インテリジェント化; トランスフェリン-PEG-リポソーム; Oxaliplatin

We performed the research works for enhancement the therapeutic effects of anti-cancer agents with the selective transfection of transporter genes into cancer cells in tumor bearing bodies. We elongated survival days with the administrations of Cisplatin entrapped transfferin binding PEG liposome for cancer peritonitis of gastric cancers, and with Oxaliplatin entrapped transfferin binding PEG liposome for cancer peritonitis of pancreatic cancers. We also developed the gene delivery systems of transporter genes. Anionic polyethylene glycol(PEG-C) binding polyethyleneimine with JTS-1, an pH sensitive fusogenic peptide was showed the enhancement of expression efficiency of Luciferase gene(6 x 10E9 RLU/mg protein). In the analysis of DNA microarray comparing with oxaliplatin sensitive cancer cell lines and resistant cancer cell lines, Tublin specific chaperon and CBP/P300-Interacting Transactivator (CITED2) genes were enhanced in the resistant cell lines. PEPT1, OATP-C and OCTN1 genes were founded with the analysis of transporter genes. PEPT1 is related the absorption of βlactum antibiotics, inhibitor of angiotensin converting enzyme, vestatin. OATP-C is related with exflux of peptide of hepatocytes. OCTN-1 is related to movement of pH dependent cationic electorates.

本课题通过选择性地将转运蛋白基因转染到荷瘤体的癌细胞中，以提高抗癌药物的治疗效果。我们用顺铂包封的transferin结合PEG脂质体治疗胃癌的癌性腹膜炎，用奥沙利铂包封的transferin结合PEG脂质体治疗胰腺癌的癌性腹膜炎，延长了生存期。我们还开发了转运基因的基因递送系统。将聚乙烯亚胺与pH敏感的融合肽JTS-1结合的阴离子聚乙二醇（PEG-C）显示荧光素酶基因的表达效率提高（6x 10 E9 RLU/mg蛋白）。在基因芯片分析中，与奥沙利铂敏感细胞系和耐药细胞系相比，Tublin特异性伴侣和CBP/P300相互作用反式激活因子（CITED 2）基因在耐药细胞系中表达增强。通过对转运蛋白基因的分析，发现了PEPT 1、OATP-C和OCTN 1基因。PEPT 1与β内酰胺类抗生素、血管紧张素转换酶抑制剂、vestatin的吸收有关。OATP-C与肝细胞肽的外排有关。OCTN-1与pH依赖性阳离子电子体的运动有关。

项目成果

Gene therapy for liver metastasis of colon cancer

结肠癌肝转移的基因治疗

• 发表时间: 2003
• 期刊: GEKARINSYO 58
• 作者: Yonezawa K;Hironobu Yanagie
• 通讯作者: Hironobu Yanagie

Involvement of OCTN1 (SLC22A4) in pH-Dependent Transport of Organic

OCTN1 (SLC22A4) 参与 pH 依赖性有机物运输

• 发表时间: 2003
• 期刊: Molecular Pharmaceutidcs Vol.11, No.1
• 作者: Ikumi Tamai

Kazuo Maruyama: "Intracellular targeting of sodium mercaptoundecahydrododecaborate (BHS) to solid tumors by transferring-PEG liposomes, for boron neutron-capture therapy (BNCT)"J.Control.Release. (in press). (2004)

Kazuo Maruyama：“通过转移 PEG 脂质体将巯基十一氢十二硼酸钠 (BHS) 细胞内靶向实体瘤，用于硼中子捕获疗法 (BNCT)”J.Control.Release。

Choronotherapy for cancer

癌症的脉络膜疗法

• 发表时间: 2003
• 期刊: Biomed Pharmacother 57
• 作者: Hironobu Yanagie

柳衛 宏宣: "大腸癌転移に対する遺伝子治療の現状と将来"臨床外科. 58. 793-798 (2003)

Hironobu Yanagie：“结直肠癌转移基因治疗的现状和未来”《临床外科》58. 793-798 (2003)。