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Molecular scaffolds as double targeting agents for the diagnosis and treatment of Neuroblastoma.

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The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as some of the most important challenges in nanomedicine field. The cellular selectivity of nanocarriers is usually achieved by their surface decoration with targeting moieties able to recognize these cells in a specific manner. Neuroblastoma (NB) is the most frequent extra-cranial pedriatic tumor, almost incurable at advanced stages. Meta-iodo-benzilguanidine (MIBG) is widely used for the diagnosis of this disease due to its strong affinity by the norepinephrine transporter (NET) usually overexpressed on the membrane of the malignant cells. Herein, a complete family of novel Y-shaped scaffolds which contains structural MIBG analogues covalently attached in each end of the Y-structure has been synthesized. The enhanced cellular uptake capacities of these double-targeting ligands have been evaluated in vitro and in vivo yielding one specific Y-shape structure which presents capacity to be engulfed by the malignant cells and be accumulated in the tumoral tissue, significantly higher than the structure which contains only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current and treatment diagnosis of this disease.
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RESEARCHER ID L-2250-2014 (Gonzalo Villaverde Cantizano) ORCID 0000-0003-2065-0417 (Gonzalo Villaverde Cantizano) RESEARCH ID L-2854-2014  (Rafael Castillo Romero) ORCID 0000-0003-1957-3098 (Rafael Castillo Romero) RESEARCHER ID K-8193-2014 (Alejandro Baeza) ORCID 0000-0002-9042-8865 (Alejandro Baeza) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)
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