title: Site-directed delivery of nitric oxide to cancers.
abstract: Nitric oxide (NO) is a reactive gaseous free radical which mediates numerous biological processes. At elevated levels, NO is found to be toxic to cancers and hence, a number of strategies for site-directed delivery of NO to cancers are in development during the past two decades. More recently, the focus of research has been to, in conjunction with other cancer drugs deliver NO to cancers for its secondary effects including inhibition of cellular drug efflux pumps. Among the various approaches toward site-selective delivery of exogenous NO sources, enzyme activated nitric oxide donors belonging to the diazeniumdiolate category afford unique advantages including exquisite control of rates of NO generation and selectivity of NO production. For this prodrug approach, enzymes including esterase, glutathione/glutathione S-transferase, DT-diaphorase, and nitroreductase are utilized. Here, we review the design and development of various approaches to enzymatic site-directed delivery of NO to cancers and their potential.
authors.affiliation: Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune, 411 008 Maharashtra, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune, 411 008 Maharashtra, India. Electronic address: harinath@iiserpune.ac.in.
authors.forename: Harinath
authors.initials: H
authors.lastname: Chakrapani
mesh_terms: D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use
chemical_list: D011355:Prodrugs; D009569:Nitric Oxide
keywords: Diazeniumdiolate; Drug delivery; Enzyme; Glutathione; Prodrug