Co-delivery of doxorubicin and aptamer against Forkhead box M1 using chitosan-gold nanoparticles coated with nucleolin aptamer for synergistic treatment of cancer cells

Abstract

Herein, a nanotherapeutic delivery method was presented for co-delivery of doxorubicin (DOX) and aptamer against Forkhead box M1 (FOXM1 Apt) to cancer cells. Firstly, the vehicle composed of chitosan (CS)-Gold nanoparticles (AuNPs) conjugate was prepared. Nucleolin aptamer (AS1411) and FOXM1 Apt were loaded onto the CS-AuNPs and formed Aptamers (Apts)-CS-AuNPs. Subsequently, DOX was added to the Apts-CS-AuNPs to obtain the DOX-Apts-CS-AuNPs complex for synergistic treatment of tumor. The data of flow cytometry analysis and fluorescence imaging displayed that the complex was effectively internalized into target cells (A549 and 4T1 cells, nucleolin+) but not into CHO cells as nontarget cells. The results of the MTT assay showed that the complex significantly increased cell mortality in 4T1 and A549 cells compared to CHO cells treated with the complex. The in vivo studies demonstrated that the DOX-Apts-CS-AuNPs complex exhibited more tumor inhibitory effect and less distribution in other organs compared to free DOX.