title: Targeted brain delivery nanoparticles for malignant gliomas.
abstract: Brain tumors display the highest mortality rates of all childhood cancers, and over the last decade its prevalence has steadily increased in elderly. To date, effective treatments for brain tumors and particularly for malignant gliomas remain a challenge mainly due to the low permeability and high selectivity of the blood-brain barrier (BBB) to conventional anticancer drugs. In recent years, the elucidation of the cellular mechanisms involved in the transport of substances into the brain has boosted the development of therapeutic-targeted nanoparticles (NPs) with the ability to cross the BBB. Here, we present a comprehensive overview of the available therapeutic strategies developed against malignant gliomas based on 'actively targeted' NPs, the challenges of crossing the BBB and blood-brain tumor barrier as well as its mechanisms and a critical assessment of clinical studies that have used targeted NPs for the treatment of malignant gliomas. Finally, we discuss the potential of actively targeted NP-based strategies in clinical settings, its possible side effects and future directions for therapeutic applications. First draft submitted: 4 October 2016; Accepted for publication: 14 October 2016; Published online: 23 November 2016.
authors.affiliation: Laboratory of Immunology of Reproduction, Faculty of Chemistry & Biology, Universidad de Santiago de Chile, 9170022 Santiago, Chile.
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Pinto
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDiS), Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Arce
authors.affiliation: Laboratory of Nanomedicine & Biomaterials, Department of Anesthesiology, Harvard Medical School, Brigham & Women's Hospital, Boston, MA 02115, USA.|Department of Chemistry, SBA School of Science & Engineering, Lahore University of Management Sciences (LUMS), Lahore 54792, Pakistan.
authors.forename: Basit
authors.initials: B
authors.lastname: Yameen
authors.affiliation: Laboratory of Nanomedicine & Targeted Delivery, Center for Integrative Medicine & Innovative Science, Faculty of Medicine, Universidad Andres Bello, Santiago, 8370071 Santiago, Chile.|Center for Bioinformatics & Integrative Biology, Faculty of Biological Sciences, Universidad Andres Bello, Santiago, 8370071 Santiago, Chile.|Center for the Development of Nanoscience & Nanotechnology, CEDENNA, 9170124 Santiago, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Vilos
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D053758:Nanoparticles
chemical_list: D000970:Antineoplastic Agents
keywords: blood–brain barrier; blood–brain tumor barrier; drug delivery; gliomas; malignant gliomas; nanomedicine; targeted nanoparticles