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

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 99mTc. Conclusion: Tumor reduction was achieved in vivo when using silver/alisertib@PNPs–chlorotoxin.

LOCATELLI Erica;  NADDAKA Maria;  UBOLDI Chiara;  LOUDOS George;  FRAGOGEORGI Eirini;  MOLINARI Valerio;  PUCCI Andrea;  TSOTAKOS Theodoros;  PSIMADAS Dimitrios;  PONTI Jessica;  COMES FRANCHINI Mauro; 

2014-07-09

FUTURE MEDICINE LTD

JRC84754

1743-5889,   

http://www.futuremedicine.com/doi/abs/10.2217/nnm.14.1,    https://publications.jrc.ec.europa.eu/repository/handle/JRC84754,   

10.2217/NNM.14.1,