title: Cytochrome P450 Bioconjugate as a Nanovehicle for Improved Chemotherapy Treatment.
abstract: Cancer is still a growing public health problem, especially breast cancer that is one of the most important cancers in women. Chemotherapy, even though a successful treatment, is accompanied by severe side effects. Moreover, most of the drugs used for chemotherapy are administered as prodrugs and need to be transformed to the active form by cytochromes P450 (CYPs). In addition, increasing numbers of cancer tissues show lower CYP activity than the surrounding healthy tissues in which prodrugs are preferentially activated causing cytotoxicity. Here, the design of a functionalized cytochrome P450 bioconjugate is reported as nanovehicle for the enzyme direct delivery to the tumor tissue in order to improve the local drug activation. MCF-7 breast cancer cells are treated with CYP-polyethylene glycol bioconjugate functionalized folic acid, where it activates the prodrug tamoxifen and significantly reduces the dose of tamoxifen needed to kill the tumor cells. The CYP bioconjugate covered with polyethylene glycol shows no immunogenic activity. The advantages of increasing the site-specific CYP activity in tumor tissues are discussed.
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km 107 carretera Tijuana-Ensenada, Ensenada, Baja California, 22760, Mexico.
authors.forename: Katrin
authors.initials: K
authors.lastname: Quester
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km 107 carretera Tijuana-Ensenada, Ensenada, Baja California, 22760, Mexico.|CONACYT Research Fellow at Centro de Nanociencias y Nanotecnología, UNAM, Ensenada, Baja California, 22760, Mexico.
authors.forename: Karla
authors.initials: K
authors.lastname: Juarez-Moreno
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, Mexico.
authors.forename: Isamel
authors.initials: I
authors.lastname: Secundino
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, Mexico.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Roseinstein
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km 107 carretera Tijuana-Ensenada, Ensenada, Baja California, 22760, Mexico.
authors.forename: Karla P
authors.initials: KP
authors.lastname: Alejo
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km 107 carretera Tijuana-Ensenada, Ensenada, Baja California, 22760, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Huerta-Saquero
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km 107 carretera Tijuana-Ensenada, Ensenada, Baja California, 22760, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vazquez-Duhalt
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D036103:Nanotechnology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D003577:Cytochrome P-450 Enzyme System
keywords: chemotherapy; cytochrome P450; functionalized PEG; prodrug activation; tamoxifen