ラジカル含有ナノ粒子の経口投与法による潰瘍性大腸炎治療と大腸癌の予防

口服含自由基纳米粒子治疗溃疡性结肠炎和预防结直肠癌

• 批准号: 13J00906
• 负责人: VONG BINHLONG (2014)
• 金额: $ 1.15万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2013
• 资助国家: 日本
• 起止时间: 2013-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13J00906/
• 关键词: oral nanotherapeutics; redox nanoparticle; reactive oxygen species; colon cancer; inflammation; side effect; ulcerative colitis; drug delivery system

Motivation and Objective: Ulcerative colitis (UC), an inflammatory and intractable disease in colon area, affects millions of patients worldwide. Moreover, UC increases the risk of the development of colitis-associated colon cancer.Oral chemotherapy is the preferred treatment for colon cancer. However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nanoparticle (RNP) that is an ideal oral therapeutics for colitis-associated colon cancer treatment.Results: RNP possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNP highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNP, no noticeable toxicities were observed in major organs of mice. Because RNP effectively scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNP with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract.Conclusion: RNP is promising oral nanotherapeutics for UC and colon cancer treatment.

动机和目的：溃疡性结肠炎（UC）是结肠区域的一种炎症性难治性疾病，影响着全世界数百万患者。此外，UC会增加患结肠炎相关结肠癌的风险。口服化疗是结肠癌的首选治疗方法。然而，该策略面临许多挑战，包括胃肠道不稳定、生物利用度不足、肿瘤靶向性低和严重的不良反应。在这项研究中，我们设计了一种新型氧化还原纳米颗粒（RNP），它是治疗结肠炎相关结肠癌的理想口服疗法。结果：RNP 核心具有硝基氧自由基，可作为活性氧（ROS）清除剂。口服RNP在结肠粘膜中高度积累，并在癌组织中特异性内化，但在正常组织中较少。尽管长期口服RNP，但在小鼠主要器官中未观察到明显的毒性。由于RNP有效清除ROS，在肿瘤部位积累后显着抑制肿瘤生长。 RNP与常规化疗药物伊立替康联合应用，可显着提高治疗效果，并有效抑制其对胃肠道的不良影响。结论：RNP是治疗UC和结肠癌的有前景的口服纳米药物。

项目成果

Nanomedicine for treatment of oxidative stress injuries. Book chapter of Post-genomic Approaches in Cancer and Nano Medicine

用于治疗氧化应激损伤的纳米药物。

• 发表时间: 2015
• 作者: Yoshitomi Toru;Vong Long Binh;Nagasaki Yukio
• 通讯作者: Nagasaki Yukio

Orally administered redox nanoparticles internalize in the inflamed tissue and prevent the colitis-associated colon cancer

口服氧化还原纳米颗粒可内化发炎组织并预防结肠炎相关的结肠癌

• 发表时间: 2014
• 作者: Long Binh Vong;Toru Yoshitomi;Hirofumi Matsui;Yukio Nagasaki
• 通讯作者: Yukio Nagasaki

Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer

• DOI: 10.1016/j.biomaterials.2015.03.037
• 发表时间: 2015-07-01
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Long Binh Vong;Yoshitomi, Toru;Nagasaki, Yukio
• 通讯作者: Nagasaki, Yukio

Indomethacin-loaded redox nanoparticles improve oral bioavailability of indomethacin and suppress its small intestinal inflammation

负载吲哚美辛的氧化还原纳米粒子提高吲哚美辛的口服生物利用度并抑制其小肠炎症

• DOI: 10.4155/tde.13.133
• 发表时间: 2014
• 期刊: Therapeutic Delivery
• 影响因子: 4.2
• 作者: Toru Yoshitomi;Sha Sha;Long Binh Vong;Pennapa Chonp athompikunlert;Hirofumi Matsui;Yukio Nagasaki
• 通讯作者: Yukio Nagasaki

Oral nanotherapeutics : Redox nanoparticles accumulate in colonic mucosa and suppress the inflammation in colitis mice

口服纳米疗法：氧化还原纳米颗粒积聚在结肠粘膜中并抑制结肠炎小鼠的炎症

• 发表时间: 2014
• 作者: Long Binh Vong;Toru Yoshitomi;Hirofumi Matsui;Yukio Nagasaki
• 通讯作者: Yukio Nagasaki