Tumor cell-specific prodrugs using arsonic acid-presenting iron oxide nanoparticles with high sensitivity

• Published in: Bioorganic & medicinal chemistry 2012-08, Vol.20 (15), p.4675-4679
• Main Authors: Minehara, Hiroki, Narita, Asako, Naka, Kensuke, Tanaka, Kazuo, Chujo, Moeko, Nagao, Masaya, Chujo, Yoshiki
• Format: Article
• Language: English
• Subjects: Animals; Anticancer drug; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; arsenic; Arsenicals - chemistry; Arsenicals - pharmacology; Arsonic acid; Biological and medical sciences; Cell Survival - drug effects; chemistry; cytotoxicity; dithiothreitol; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ferric Compounds - chemical synthesis; Ferric Compounds - chemistry; Ferric Compounds - pharmacology; glutathione; HeLa Cells; Hep G2 Cells; hepatocytes; Hepatocytes - drug effects; Humans; Iron oxide; iron oxides; magnetic resonance imaging; Medical sciences; Mice; Nanoparticle; nanoparticles; Nanoparticles - chemistry; Pharmacology. Drug treatments; Prodrug; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacology; Structure-Activity Relationship; viability
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.06.012

We report the tumor cell-selective prodrugs based on the arsonic acid-presenting iron oxide nanoparticles. We synthesized the well-dispersed nanoparticles having arsonoacetic acid which is composed of the low toxic As(V) form. From the analyses of the reaction products, it is suggested that the reduction by dithiothreitol with arsonoacetic acid and the modified nanoparticles could generate the highly-toxic As(III) species. In the MTT assays, it was found that the cell viabilities of HeLaS3 and especially HepG2 were reduced in the presence of the modified nanoparticles. In contrast, a slight effect on viability was observed with primary mouse hepatocytes. The viabilities showed good agreements with the amounts of intracellular reduced glutathione concentrations. Furthermore, the valid concentrations of the modified nanoparticles for tumor-specific cytotoxicity were similar level in MRI measurements. These results indicate that arsonic acid-presenting nanoparticles should be a good platform for developing highly-sensitive tumor-specific prodrugs.