Abstract
Excess generation of reactive oxygen species (ROS) in colonic mucosa of patients with ulcerative colitis (UC), a type of inflammatory bowel disease, causes the inflammation, risk of colitis-associated colon cancer (CAC), and drug resistance. Oral administration is more convenient for patients; however, current medications for UC are not effective due to instability in the gastrointestinal (GI) tract, non-specific distribution, and adverse effects. To address these issues, we have developed novel oral redox nanoparticles (RNP), which was prepared by self-assembly of an amphiphilic block copolymer with stable nitroxide radicals, ROS scavengers, in a hydrophobic segment as a side chain via an ether linkage. After oral administration, RNP highly accumulated in colon region, and specifically diffused into colonic mucosa of inflamed sites. Orally administered RNP effectively scavenged overproduced ROS in the inflamed colon, resulting in suppression of inflammation in mice model of colitis. Interestingly, when anticancer drug irinotecan (Iri) was administered in combination with RNP, a remarkable suppression of tumor growth was observed in CAC model mice treated with combination compared to mice treated with Iri alone. Iri-induced adverse effects, such as diarrhea and GI inflammation, were remarkably reduced by RNP treatment. Toxicity evaluation on zebrafish embryos showed that TEMPOL induces severe mitochondrial dysfunction, leading to the dead of all zebrafish embryos while RNP did not cause mitochondrial dysfunction in zebrafish embryos, and no zebrafish dead was observed, indicating that RNP did not disturb intracelluar redox balance. RNP is a promising nanotherapeutics for treatment of UC and other ROS-related diseases.
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Acknowledgements
Author would like to express his sincere appreciation to Prof. Nagasaki Yukio (University of Tsukuba) and  all collaborators for their supports and valuable advices, and funding from Japan Society for the Promotion of Science (JSPS) for Young Scientist. This work was also partly supported by Vietnam National Foundation for Science and Technology Development (NAFOSTED under Grant number 108.05-2017.327 to L.B. Vong).
Conflict of Interest The authors declare that they have no conflict of interest.
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Vong, L.B., Nagasaki, Y. (2020). Redox Polymeric Nanoparticle as an Effective Oral Nanotherapeutics for Inflammatory Bowel Disease and Cancer. In: Van Toi , V., Le, T., Ngo, H., Nguyen, TH. (eds) 7th International Conference on the Development of Biomedical Engineering in Vietnam (BME7). BME 2018. IFMBE Proceedings, vol 69. Springer, Singapore. https://doi.org/10.1007/978-981-13-5859-3_31
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DOI: https://doi.org/10.1007/978-981-13-5859-3_31
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