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

摘要

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.