Newly Designed Silica-Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer

• Published in: Advanced healthcare materials Vol. 6; no. 20
• Main Authors: Vong, Long Binh, Kimura, Shinya, Nagasaki, Yukio
• Format: Journal Article
• Language: English
• Published: Germany 01.10.2017
• Subjects: Administration, Oral; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Area Under Curve; Cell Line, Tumor; Cell Survival - drug effects; Colitis - chemically induced; Colitis - complications; Colonic Neoplasms - drug therapy; Colonic Neoplasms - etiology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Coumarins - chemistry; Coumarins - pharmacokinetics; Coumarins - pharmacology; Coumarins - therapeutic use; DNA Topoisomerases, Type II - metabolism; Drug Carriers - chemistry; Half-Life; Humans; Male; Mice; Mice, Inbred ICR; Nanoparticles - chemistry; Oxidation-Reduction; Poly-ADP-Ribose Binding Proteins - antagonists & inhibitors; Poly-ADP-Ribose Binding Proteins - metabolism; Polymers - chemistry; Quinolines - chemistry; Quinolines - pharmacokinetics; Quinolines - pharmacology; Quinolines - therapeutic use; Reactive Oxygen Species - metabolism; ROC Curve; Silicon Dioxide - chemistry; cancer therapy; reactive oxygen species (ROS); adverse effect; oral drug delivery; redox nanoparticles
• ISSN: 2192-2659
• DOI: 10.1002/adhm.201700428

Although oral drug delivery is the most common route of drug administration, the conventional polymeric nanocarriers exhibit a low drug loading capacity and low stability in the gastrointestinal (GI) environments. In this study, a newly designed silica-containing redox nanoparticle (siRNP) with reactive oxygen species (ROS) scavenging capacity is developed as an ideal oral nanocarrier for a novel hydrophobic anticancer compound BNS-22 to treat colitis-associated colon cancer in vivo. Crosslinking of silica moieties significantly enhances the stability under acidic conditions and improves BNS-22 loading capacity of siRNP compared to the conventional redox nanoparticle. After oral administration to mice, BNS-22-loaded siRNP (BNS-22@siRNP) remarkably improves bioavailability and colonic tumor distribution of BNS-22. As the result, BNS-22@siRNP significantly inhibits the tumor progression in colitis-associated colon cancer mice compared to other control treatments. It is noteworthy that no systemic absorption of siRNP carrier is observed after oral administration. Interestingly, orally administered BNS-22@siRNP significantly suppresses the adverse effects of BNS-22 owing to its ROS scavenging capacity, and no other noticeable toxicities are observed in mice treated with BNS-22@siRNP although siRNP is localized in the GI tract. Our results indicate that siRNP is a promising oral drug nanocarrier for cancer therapy.