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

Original submitted 8 April 2013; Revised submitted 19 December 2013

Keywords::

• alisertib
• cancer
• glioblastoma
• nanoprecipitation
• organic coating
• polymeric nanoparticle
• radiolabeling
• silver nanoparticle
• toxicity
• tumor reduction

Financial & competing interests disclosure

This work was supported by the University of Bologna. This work was also supported by the Work program Action 15024: Nanobiotechnologies of DG Joint Research Centre. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the University of Bologna. This work was also supported by the Work program Action 15024: Nanobiotechnologies of DG Joint Research Centre. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.