Development of an oral nanotherapeutics using redox nanoparticles for treatment 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(O)) that is an ideal oral therapeutics for colitis-associated colon cancer treatment. RNP(O) possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNP(O) highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNP(O), no noticeable toxicities were observed in major organs of mice. Because RNP(O) effectively scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNP(O) with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract. Therefore, RNP(O) is promising oral nanotherapeutics for cancer therapies.
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8573, Japan.
Long Binh
LB
Vong
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8573, Japan.
Toru
T
Yoshitomi
Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan; Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Hirofumi
H
Matsui
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8573, Japan. Electronic address: yukio@nagalabo.jp.
Yukio
Y
Nagasaki
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D001397:Azoxymethane / Q000008:administration & dosage; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D003092:Colitis / Q000150:complications / Q000628:therapy*; D003110:Colonic Neoplasms / Q000150:complications / Q000628:therapy*; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004724:Endoscopy; D016166:Free Radical Scavengers / Q000737:chemistry*; D007249:Inflammation / Q000473:pathology; D000077146:Irinotecan; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000628:therapy; D009589:Nitrogen Oxides / Q000737:chemistry; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry
D000970:Antineoplastic Agents; D003911:Dextrans; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D013431:Sulfates; C012036:sodium sulfate; D000077146:Irinotecan; C039900:nitroxyl; D001397:Azoxymethane; D002166:Camptothecin
Cancer; Drug delivery system; Oral therapeutics; ROS; Redox nanoparticles