Targeted Delivery of Silver Nanoparticles and Alisertib:In VitroandIn VivoSynergistic Effect Against Glioblastoma

• DOI: 10.2217/nnm.14.1
• Publication Date: 2014-01-17T09:14:43Z
• Authors: Erica Locatelli; Maria Naddaka; Chiara Uboldi; George Loudos; Eirini Fragogeorgi; Valerio Molinari; Andrea Pucci; Theodoros Tsotakos; Dimitrios Psimadas; Jessica Ponti; Mauro Comes Franc...
• Keywords: radiolabeling; 0301 basic medicine; Silver; Polymers; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; tumor reduction; Scorpion Venoms; [SDV.CAN]Life Sciences [q-bio]/Cancer; Antineoplastic Agents; nanoprecipitation; Mice; 03 medical and health sciences; Drug Delivery Systems; Cell Line, Tumor; cancer; Animals; Humans; Tissue Distribution; organic coating; alisertib; glioblastoma; silver nanoparticle; Brain Neoplasms; glioblastoma; toxicity; Drug Synergism; silver nanoparticle; Azepines; 3. Good health; alisertib; Pyrimidines; [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; Nanoparticles; polymeric nanoparticle; Glioblastoma

Targeted biocompatible nanoplatforms presenting multiple therapeutic functions have great potential for the treatment of cancer.Multifunctional nanocomposites formed by polymeric nanoparticles (PNPs) containing two cytotoxic agents - the drug alisertib and silver nanoparticles - were synthesized. These PNPs have been conjugated with a chlorotoxin, an active targeting 36-amino acid-long peptide that specifically binds to MMP-2, a receptor overexpressed by brain cancer cells.The individual and synergistic activity of these two cytotoxic agents against glioblastoma multiforme was tested both in vitro and in vivo. The induced cytotoxicity in a human glioblastoma-astrocytoma epithelial-like cell line (U87MG) was studied in vitro through a trypan blue exclusion test after 48 and 72 h of exposure. Subsequently, the PNPs' biodistribution in healthy animals and their effect on tumor reduction in tumor-bearing mice were studied using PNPs radiolabeled with (99m)Tc.Tumor reduction was achieved in vivo when using silver/alisertib@PNPs-chlorotoxin.