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

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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.