Active targeting co-delivery of therapeutic Sur siRNA and an antineoplastic drug via epidermal growth factor receptor-mediated magnetic nanoparticles for synergistic programmed cell death in glioblastoma stem cells

Abstract

Active targeting co-delivery of therapeutic siRNAs and antineoplastic drugs is considered as a very promising approach to specifically improve the therapeutic effect by simultaneously inhibiting the expression of tumorigenic genes and reducing the systemic toxicity of anticancer drugs. This strategy for effectively targeting cancer stem cells (CSCs) has gained considerable attention in the therapeutic treatment of human cancers. The objective of this study was to fabricate and characterize the therapeutic survivin siRNAs (Sur siRNA) and anti-cancer drug doxorubicin (DOX)-loaded superparamagnetic iron oxide nanoparticles (SPIONPs) that are surface-conjugated to the specific ligand epidermal growth factor receptor (EGFR) which is highly expressed on brain glioblastoma stem cells (GSCs), using carboxymethyl chitosan (CMCS), polyethylenimine (PEI) and heparin-mediated cross linking agents. Our in vitro and in vivo studies demonstrated that the fabricated EGFR-targeted nanoparticles exhibited excellent targeting specificity and enhanced delivery efficiency, and could specifically co-deliver therapeutic siRNAs and DOX into GSCs, thus greatly improving the therapeutic efficacy by effectively silencing survivin gene expression and enhancing the treatment sensitivity of GSCs to anticancer drug DOX. Therefore, these fabricated EGFR-targeted nanoparticles would provide an efficient targeting vector for co-delivery of therapeutic siRNAs and anticancer drugs, and could be used as a promising active targeted nanocarrier for the selective treatment of human brain cancer in the future.