title: Targeted delivery of silver nanoparticles and alisertib: in vitro and in vivo synergistic effect against glioblastoma.
abstract: OBJECTIVE
  Targeted biocompatible nanoplatforms presenting multiple therapeutic functions have great potential for the treatment of cancer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Tumor reduction was achieved in vivo when using silver/alisertib@PNPs-chlorotoxin.
authors.affiliation: Department of Industrial Chemistry, "TosoMontanari", University of Bologna, Via Risorgimento 4, 40136, Bologna, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Locatelli
authors.forename: Maria
authors.initials: M
authors.lastname: Naddaka
authors.forename: Chiara
authors.initials: C
authors.lastname: Uboldi
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.forename: Eirini
authors.initials: E
authors.lastname: Fragogeorgi
authors.forename: Valerio
authors.initials: V
authors.lastname: Molinari
authors.forename: Andrea
authors.initials: A
authors.lastname: Pucci
authors.forename: Theodoros
authors.initials: T
authors.lastname: Tsotakos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Psimadas
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponti
authors.forename: Mauro Comes
authors.initials: MC
authors.lastname: Franchini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001381:Azepines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism; D012834:Silver / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; C550258:MLN 8237; D011108:Polymers; D011743:Pyrimidines; D012604:Scorpion Venoms; C091539:Chlorotoxin; D012834:Silver
keywords: alisertib; cancer; glioblastoma; nanoprecipitation; organic coating; polymeric nanoparticle; radiolabeling; silver nanoparticle; toxicity; tumor reduction