Premium
Cytochrome P450 Bioconjugate as a Nanovehicle for Improved Chemotherapy Treatment
Author(s) -
Quester Katrin,
JuarezMoreno Karla,
Secundino Isamel,
Roseinstein Yvonne,
Alejo Karla P.,
HuertaSaquero Alejandro,
VazquezDuhalt Rafael
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201600374
Subject(s) - bioconjugation , chemistry , cytochrome p450 , chemotherapy , pharmacology , cancer research , biophysics , medicine , biochemistry , enzyme , biology
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.