title: Double Sequential Encrypted Targeting Sequence: A New Concept for Bone Cancer Treatment.
abstract: The selective transportation of therapeutic agents to tumoral cells is usually achieved by their conjugation with targeting moieties able to recognize these cells. Unfortunately, simple and static targeting systems usually show a lack in selectivity. Herein, a double sequential encrypted targeting system is proposed as a stimuli-responsive targeting analogue for selectivity enhancement. The system is able to recognize diseased bone tissue in the first place, and once there, a hidden secondary targeting group is activated by the presence of an enzyme overproduced in the malignant tissue (cathepsin K), thereby triggering the recognition of diseased cells. Transporting the cell targeting agent in a hidden conformation that contains a high selective tissular primary targeting, could avoid not only its binding to similar cell receptors but also the apparition of the binding-site barrier effect, which can enhance the penetration of the therapeutic agent within the affected zone. This strategy could be applied not only to conjugate drugs but also to drug-loaded nanocarriers to improve the efficiency for bone cancer treatments.
authors.affiliation: Depto. Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid. Plaza Ramon y CajaLs/n. Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 ¡ Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Villaverde
authors.affiliation: Depto. Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid. Plaza Ramon y CajaLs/n. Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 ¡ Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nairi
authors.affiliation: Depto. Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid. Plaza Ramon y CajaLs/n. Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 ¡ Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Baeza
authors.affiliation: Depto. Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid. Plaza Ramon y CajaLs/n. Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 ¡ Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vallet-Regí
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D056657:Cathepsin K / Q000378:metabolism; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid; D056657:Cathepsin K
keywords: cancer; drug delivery; dual targeting; encrypted peptide; stimuli-responsive targeting