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 (99m)Tc.

CONCLUSION

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