Liposomal surface-loading of water-soluble cationic iron(III) porphyrins as anticancer drugs.
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.
Yuasa
Makoto
M
Department of Pure & Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, Noda 278-8510, Japan. yuasa@rs.noda.tus.ac.jp
Oyaizu
Kenichi
K
Horiuchi
Aiko
A
Ogata
Akihiko
A
Hatsugai
Tomomi
T
Yamaguchi
Aritomo
A
Kawakami
Hiroyoshi
H
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors; D002384:Catalysis; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism*; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D012995:Solubility; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D013499:Surface Properties; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D002412:Cations; D005290:Ferric Compounds; D005609:Free Radicals; D008081:Liposomes; D008665:Metalloporphyrins; D014867:Water; D002374:Catalase; D013482:Superoxide Dismutase