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Newly Designed Silica‐Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer
Author(s) -
Vong Long Binh,
Kimura Shinya,
Nagasaki Yukio
Publication year - 2017
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201700428
Subject(s) - nanocarriers , oral administration , bioavailability , pharmacology , cancer , drug delivery , drug , systemic administration , in vivo , drug carrier , reactive oxygen species , medicine , chemistry , cancer research , biochemistry , biology , organic chemistry , microbiology and biotechnology
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.