Active Targeting Co-Delivery of Therapeutic <i>Sur</i> siRNA and 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 in a targeted manner to improve therapeutic effects via simultaneously repressing expression of tumorigenic genes and reducing the systemic toxicity of the anticancer drugs. The development of such strategies that could efficiently target cancer stem cells (CSCs) has gained considerable attention in the therapeutic treatments of human cancers. The objective of this study was to prepare and characterize the therapeutic survivin siRNAs (Sur siRNA) and anti-cancer drug doxorubicin (DOX) loaded superparamagnetic iron oxide nanoparticles (SPIO NPs) that were surface conjugated with the specific ligand to epidermal growth factor receptor (EGFR), highly expressed on brain glioblastoma stem cells (GSCs), using carboxymethyl chitosan (CMCS), polyethylenimine (PEI) and heparin mediated cross linking agents. This prepared EGFR-targeted nanoparticles exhibited excellent targeting specificity and enhanced delivery efficiency, and could specifically co-deliver therapeutic siRNAs and DOX into GSCs, and thus greatly improved the therapeutic efficacy by effectively silencing of survivin gene expression and enhanced the treatment sensitivity of GSCs to anticancer drug DOX. Therefore, these fabricated EGFR-targeted nanoparticles provided an efficient targeted vehicle for co-delivery of therapeutic siRNAs and anticancer drugs, and could serve as a promising active targeting nanocarrier for selective therapeutic treatments of human brain cancer in future.