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New targeting agent for the selective drug delivery of nanocarriers for treating neuroblastoma

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Villaverde, Gonzalo and Baeza, Alejandro and Melen, Gustavo J. and Alfranca, Arantzazu and Ramirez, Manuel and Vallet Regí, María (2015) New targeting agent for the selective drug delivery of nanocarriers for treating neuroblastoma. Journal of Materials Chemistry B, 3 (24). pp. 4831-4842. ISSN 2050-750X

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Abstract

Novel targeting agents against neuroblastoma based on the meta-iodobenzylguanidine (MIBG) moiety were synthesized and biologically evaluated for nanocarrier vectorization. These compounds have been anchored on the surface of drug loaded mesoporous silica nanocarriers, resulting in the improved cellular uptake in tumoral cells. Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Advanced forms of the disease (metastatic and/or refractory) have a dismal prognosis despite the combination of chemotherapy, radiotherapy, surgery and bone narrow transplants. These treatments carry severe side effects and, in some cases, compromise the life of the patient. MIBG has been widely applied in the medical diagnosis of NB due to its affinity for tumor cells through the norepinephrine transporter (NET), which is expressed in 90% of NB tumors. The exclusive accumulation of MIBG in neuroblastoma has been widely studied; however, its properties have been never exploited as a targeting agent in nanocarrier drug delivery systems. Several structural analogues of MIBG have been prepared and attached on the surface of nanocarriers. Their selective internalization has been tested against human neuroblastoma cells, which show, in the best case, cellular uptake four times higher than that of the naked nanosystem. Furthermore, in vivo experiments showed preferential and selective accumulation and retention of the targeted nanosystem comparing with the naked and only PEGylated counterpart systems. This novel nanosystem could be easily applicable to all kinds of drug delivery nanocarriers, providing a universal tool for neuroblastoma chemotherapies that is superior to classical approaches through a novel nanosystem exclusively designed to target this terrible malignancy.


Item Type:Article
Additional Information:

RESEARCH ID M-3378-2014 (María Vallet Regí)
ORCID 0000-0002-6104-4889 (María Vallet Regí)
RESEARCH ID M-3316-2014 (Antonio Salinas Sánchez)
ORCID 0000-0002-8408-3389 (Antonio Salinas Sánchez)
ORCID 0000-0003-2065-0417 (Gonzalo Villaverde Cantizano)
ResearcherID: L-2250-2014 (Gonzalo Villaverde Cantizano)

Uncontrolled Keywords:Mesoporous silica nanoparticles, M-Iodobenzylguanidine analogs, Side-chain, Norepinephrine transporter, Cancer nanomedicine, Tumor-cells, In-vivo, Fluorescent, Retention, Generation
Subjects:Sciences > Chemistry > Materials
Sciences > Chemistry > Chemistry, Inorganic
ID Code:41688
Deposited On:18 Apr 2017 12:29
Last Modified:19 Apr 2017 07:39

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