Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer
Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer
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DOI：
10.1016/j.biomaterials.2015.03.037
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发表时间：
2015-07-01
期刊：
影响因子：
14
通讯作者：
Nagasaki, Yukio
中科院分区：
文献类型：
--
作者：
Long Binh Vong;Yoshitomi, Toru;Nagasaki, Yukio
口服化疗是结肠癌的首选治疗方法。然而，这一策略面临许多挑战，包括胃肠道(GI)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，我们设计了一种新的氧化还原纳米颗粒(RNPO)，它是治疗结肠炎相关性结肠癌的理想口服疗法。RNPO的核心含有氮氧自由基，可作为活性氧自由基(ROS)的清除剂。口服RNPO后，RNPO在结肠粘膜中高度蓄积，并在癌组织中特异性内化，而在正常组织中较少。尽管长期口服RNPO，但对小鼠的主要器官没有明显的毒性。由于RNPO有效地清除了ROS，它在肿瘤部位积聚后显著抑制了肿瘤的生长。RNPO联合常规化疗伊立替康可显著提高疗效，有效抑制其对胃肠道的不良反应。因此，RNPO有望成为治疗癌症的口服纳米疗法。(C)2015爱思唯尔有限公司。保留所有权利。
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 (RNPO) that is an ideal oral therapeutics for colitis-associated colon cancer treatment. RNPO possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNPO highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNPO, no noticeable toxicities were observed in major organs of mice. Because RNPO effectively Scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNPO with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract. Therefore, RNPO is promising oral nanotherapeutics for cancer therapies. (C) 2015 Elsevier Ltd. All rights reserved.