title: Biocatalytic virus capsid as nanovehicle for enzymatic activation of Tamoxifen in tumor cells.
abstract: Most of the drugs used in chemotherapy should be activated by a transformation catalyzed by cytochrome P450 (CYP) enzymes. In this work, bacteriophage P22 virus-like particles (VLPs) containing CYP activity, immunologically inert and functionalized in order to be recognized by human cervix carcinoma cells and human breast adenocarcinoma cells were designed. The CYP was encapsulated inside the virus capsid obtained from the bacteriophage P22. CYP and coat protein were both heterologously expressed in E. coli. The VLPs with enzymatic activity were covered with polyethylene glycol that was functionalized in its distal end with folic acid in order to be recognized by folate receptors exhibited on tumor cells. The capacity of biocatalytic VLPs to be recognized and internalized into tumor cells is demonstrated. The VLP-treated cells showed enhanced capacity for the transformation of the pro-drug tamoxifen, which resulted in an increase of the cell sensitivity to this oncological drug. In this work, the potential use of biocatalytic VLPs vehicles as a delivery system of medical relevant enzymes is clearly demonstrated. In addition to cancer treatment, this technology also offers an interesting platform as nano-bioreactors for intracellular delivery of enzymatic activity for other diseases originated by the lack of enzymatic activity.
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tapia-Moreno
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, Mexico.
authors.forename: Karla
authors.initials: K
authors.lastname: Juarez-Moreno
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalez-Davis
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, Mexico.
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Cadena-Nava
authors.affiliation: Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vazquez-Duhalt
mesh_terms: D017100:Bacteriophage P22 / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D055162:Biocatalysis; D002213:Capsid / Q000737:chemistry / Q000201:enzymology*; D045744:Cell Line, Tumor; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D004789:Enzyme Activation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D013629:Tamoxifen; D011092:Polyethylene Glycols; D003577:Cytochrome P-450 Enzyme System
keywords: Chemotherapy; Cytochrome P450; Enzyme delivery; Nanoparticles; Virus-like particles