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 (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.

• Authors: Long Binh Vong, Toru Yoshitomi, Hirofumi Matsui, Yukio Nagasaki
• Journal: Biomaterials (Biomaterials) Vol. 55 Pg. 54-63 (Jul 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25934452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Dextrans
• Free Radical Scavengers
• Nitrogen Oxides
• Reactive Oxygen Species
• Sulfates
• sodium sulfate
• Irinotecan
• nitroxyl
• Azoxymethane
• Camptothecin

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (chemistry)
• Azoxymethane (administration & dosage)
• Camptothecin (analogs & derivatives, chemistry)
• Cell Line, Tumor
• Colitis (complications, therapy)
• Colonic Neoplasms (complications, therapy)
• Dextrans (chemistry)
• Drug Delivery Systems
• Drug Screening Assays, Antitumor
• Endoscopy
• Free Radical Scavengers (chemistry)
• Inflammation (pathology)
• Irinotecan
• Male
• Mice
• Mice, Inbred ICR
• Nanomedicine (methods)
• Nanoparticles (chemistry)
• Neoplasms, Experimental (therapy)
• Nitrogen Oxides (chemistry)
• Oxidation-Reduction
• Reactive Oxygen Species (chemistry)
• Sulfates (chemistry)