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

Abstract 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.