title: Synthesis of chlorin e6-transferrin and demonstration of its light-dependent in vitro breast cancer cell killing ability.
abstract: The transferrin receptor is often highly expressed in tumor cells whereas it is usually present at low levels in surrounding normal adult tissue. Here, a potential anti-cancer agent is described, which is directed at this receptor and consists of a toxin-modified transferrin, which is activated via photodynamic therapy. The porphyrin chlorin e6 was conjugated to transferrin using a procedure, which involved the preliminary binding of the protein to quaternary amino ethyl-sephadex. This maintained the natural activity of the transferrin, and the un-activated conjugate exhibited no in vitro cellular toxicity. The conjugate's singlet oxygen yield was estimated by assessment of its light-dependent oxidation of tetramethylbenzidine, where it displayed approximately 70% of the efficiency of native chlorin e6. When chlorin e6-transferrin treated human MCF7 and rat MTLn3 mammary adenocarcinoma cells were exposed to toxin-activating visible light, a tumor cell killing effect was achieved in normal (medium plus 10% FBS) culture conditions with an ED50 of approximately 10-20 microg/ml. A method for the synthesis of chlorin e6-transferrin was developed, and the conjugate was shown to exhibit a light-dependent killing of mammary adenocarcinoma cells in culture. The conjugate demonstrated potential as an anti-cancer agent.
authors.affiliation: The Institute for Molecular Medicine, Huntington Beach, CA 92649, USA. pcavanaugh@immed.org
authors.forename: Philip G
authors.initials: PG
authors.lastname: Cavanaugh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D002735:Chlorophyllides; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors / Q000187:drug effects; D014168:Transferrin / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002735:Chlorophyllides; D000922:Immunotoxins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D011990:Receptors, Transferrin; D014168:Transferrin; C062985:phytochlorin