Liposomal Surface-Loading of Water-Soluble Cationic Iron(III) Porphyrins as Anticancer Drugs

• Published in: Molecular pharmaceutics 2004-09, Vol.1 (5), p.387-389
• Main Authors: Yuasa, Makoto, Oyaizu, Kenichi, Horiuchi, Aiko, Ogata, Akihiko, Hatsugai, Tomomi, Yamaguchi, Aritomo, Kawakami, Hiroyoshi
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Carcinoma, Lewis Lung - enzymology; Carcinoma, Lewis Lung - metabolism; Catalase - antagonists & inhibitors; Catalysis; Cations - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Drug Delivery Systems - methods; Drug Design; Drug Screening Assays, Antitumor; Ferric Compounds - chemistry; Ferric Compounds - pharmacology; Free Radicals - chemistry; Free Radicals - metabolism; Liposomes - chemistry; Liposomes - metabolism; Lung Neoplasms - enzymology; Lung Neoplasms - metabolism; Metalloporphyrins - chemistry; Metalloporphyrins - pharmacology; Mice; Mice, Inbred C57BL; Models, Biological; Solubility; Superoxide Dismutase - antagonists & inhibitors; Surface Properties; Water - chemistry
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp049936v

A novel design of anticancer drug delivery system, based on an electrostatic binding of negatively charged liposomes and cationic metalloporphyrins under physiological conditions, is reported. A lack of cytotoxicity of the iron(III) porphyrin-loaded liposomes and an efficient generation of a toxic hydroxyl radical (OH•) from a superoxide anion radical (O2 -•) through the iron(III)-catalyzed dismutation and the Fenton-like reaction allow for a targeted necrosis of tumor cells where the concentration of O2 -• is locally increased as a result of the reduced activity of superoxide dismutase and catalase in these cells. Keywords: Anticancer drug delivery system; liposome; cationic metalloporphyrins; superoxide anion radical; hydroxyl radical