Targeted delivery of silver nanoparticles and alisertib: in vitro and in vivo synergistic effect against glioblastoma.

Abstract

AIM:

Targeted biocompatible nanoplatforms presenting multiple therapeutic functions have great potential for the treatment of cancer.

MATERIALS & 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.

CONCLUSION:

Tumor reduction was achieved in vivo when using silver/alisertib@PNPs-chlorotoxin.

• Authors: Erica Locatelli, Maria Naddaka, Chiara Uboldi, George Loudos, Eirini Fragogeorgi, Valerio Molinari, Andrea Pucci, Theodoros Tsotakos, Dimitrios Psimadas, Jessica Ponti, Mauro Comes Franchini
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 9 Issue 6 Pg. 839-49 (May 2014) ISSN: 1748-6963 [Electronic] England
• PMID: 24433240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Azepines
• MLN 8237
• Polymers
• Pyrimidines
• Scorpion Venoms
• Chlorotoxin
• Silver

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Azepines (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Brain Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Drug Delivery Systems
• Drug Synergism
• Glioblastoma (drug therapy, pathology)
• Humans
• Mice
• Nanoparticles (chemistry)
• Polymers (chemistry)
• Pyrimidines (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Scorpion Venoms (chemistry, metabolism)
• Silver (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Tissue Distribution