title: Nanoparticle strategies for cancer therapeutics: Nucleic acids, polyamines, bovine serum amine oxidase and iron oxide nanoparticles (Review).
abstract: Nanotechnology for cancer gene therapy is an emerging field. Nucleic acids, polyamine analogues and cytotoxic products of polyamine oxidation, generated in situ by an enzyme-catalyzed reaction, can be developed for nanotechnology-based cancer therapeutics with reduced systemic toxicity and improved therapeutic efficacy. Nucleic acid-based gene therapy approaches depend on the compaction of DNA/RNA to nanoparticles and polyamine analogues are excellent agents for the condensation of nucleic acids to nanoparticles. Polyamines and amine oxidases are found in higher levels in tumours compared to that of normal tissues. Therefore, the metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, can be targets for antineoplastic therapy since these naturally occurring alkylamines are essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. In particular, polyamine catabolism involves copper-containing amine oxidases. Several studies showed an important role of these enzymes in developmental and disease-related processes in animals through the control of polyamine homeostasis in response to normal cellular signals, drug treatment, and environmental and/or cellular stress. The production of toxic aldehydes and reactive oxygen species (ROS), H2O2 in particular, by these oxidases suggests a mechanism by which amine oxidases can be exploited as antineoplastic drug targets. The combination of bovine serum amine oxidase (BSAO) and polyamines prevents tumour growth, particularly well if the enzyme has been conjugated with a biocompatible hydrogel polymer. The findings described herein suggest that enzymatically formed cytotoxic agents activate stress signal transduction pathways, leading to apoptotic cell death. Consequently, superparamagnetic nanoparticles or other advanced nanosystem based on directed nucleic acid assemblies, polyamine-induced DNA condensation, and bovine serum amine oxidase may be proposed for futuristic anticancer therapy utilizing nucleic acids, polyamines and BSAO. BSAO based nanoparticles can be employed for the generation of cytotoxic polyamine metabolites.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome and CNR, Institute of Biology and Molecular Pathology, 00185 Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Agostinelli
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy and Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Palacky University in Olomouc, Olomouc 77146, Czech Republic.
authors.forename: Fabio
authors.initials: F
authors.lastname: Vianello
authors.affiliation: Department Organi di Senso, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magliulo
authors.affiliation: Formerly Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers the State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Thresia
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers the State University of New Jersey, New Brunswick, NJ 08901, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002417:Cattle; D042003:DNA Packaging / Q000187:drug effects; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D050997:Nanomedicine / Q000379:methods / Q000639:trends; D053758:Nanoparticles / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy*; D009696:Nucleic Acids / Q000378:metabolism / Q000494:pharmacology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000502:physiology*; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D000097667:Polyamine Oxidase
chemical_list: D005290:Ferric Compounds; D009696:Nucleic Acids; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase; C000499:ferric oxide